The community site for and by
developmental and stem cell biologists

Why Independent Antibody Reviews? 5 Problems They Overcome to Facilitate Rigor & Reproducibility

Posted by , on 5 October 2017

 

In the internet age, what’s the first thing you do before spending money on anything? Right: Go online and read reviews.

Well, the same behavior applies with buying antibodies. We look to publications like “reviews,” to ensure antibodies have produced reliable data in similar experimental contexts.

 

While sifting through publications is the gold standard for finding antibodies, however, there are some limitations. In this article, I’d like to outline these limitations and show how independent antibody reviews could address them.

 

Review Blog Cover.jpg

1. Latency Between Data Generation and Publication

 

Problem: It takes an average of 9 months from manuscript submission to publication. This delay in data availability due to the (essential) peer-review process could lead other labs to waste valuable resources testing an antibody that has already been validated.

Solution: The submission of independent reviews immediately following successful data generation would ensure that data about successful antibody usage was shared within the research community without delay.

 

2. Only Positive Results Are Published

 

Problem: For every beautiful, sharp and crisp IF image, there were probably 2-3 antibodies that were tested and didn’t work. However, such negative data are usually never published and are forever hidden in the hard drive of a lab computer.

Solution: Independent reviews can capture cases where antibodies didn’t work, to help other scientists make more informed decisions—the same way we avoid restaurants with horrific reviews.

 

3. Validation Data May Not Be Shown

 

Problem: Most labs have validated antibodies targeting their protein of interest through knock-out or knock-down experiments. Yet the validation data are not always included in the publication because it’s “not part of the story,” and are often only known to the reviewers and lab members.

Solution: The sharing of antibody validation data from every lab through reviews would generate an invaluable database of validated antibodies.

4. Limited Space for Detailed Protocol

Problem: Many journals have word limits for their publications, which in turn caps how much protocol detail you can put into the Materials & Methods. And as we all know, to conduct a successful experiment, even the tiniest detail matters.

Solution: Unbound by editorial constraints, in each antibody review full experimental protocols could be submitted to facilitate reproducibility.

 

5. Some Data Are Locked Behind Paywall

 

Problem: Approximately 76% of publications are behind paywall, and thus, the majority of published antibody usage data are not available to all scientists.

Solution: The adoption of independent reviews aligns with the recent movement towards open science, and ensures that every successful usage of antibodies is known to the entire research community.

 

 

In fact, we feel so strongly about independent antibody reviews that we’ve actually built them into BenchSci.

At BenchSci, our goal is to drive discovery by ending reagent failure. Our machine-learning technology analyzes open- and closed-access publications and presents published figures with actionable insights. At the same time, we also recognize the limitations discussed in this article, which is why we also incorporated independent antibody reviews into the platform.

With the recent emphasis on research rigor and reproducibility by the NIH, I would like to advocate for the submission of independent antibody reviews to facilitate a collective effort to authenticate key biological resources, which, in turn, would benefit the research community as a whole. If you agree, consider signing up for BenchSci free and contributing reviews.

 

Thumbs up (3 votes)
Loading...

Categories: Discussion, Research, Resources

Navigate the archive

Use our Advanced Search tool to search and filter posts by date, category, tags and authors.

Postdoc position in microRNA biology and regulation at NIH

Posted by , on 5 October 2017

Closing Date: 15 March 2021

Fully-funded postdoc positions are available in a new lab group starting at the NIH main campus in Bethesda, Maryland. Research in the McJunkin lab has two major long-term goals: 1) to define the biological functions of miRNAs during embryogenesis and 2) to elucidate mechanisms of miRNA turnover. Using C. elegans as a model organism to address these questions, we will combine the strengths of classical forward genetics with CRISPR-Cas-9-mediated genome editing, next-generation sequencing, cell biology, and biochemical techniques. Because embryonically-expressed miRNAs exhibit a sharp decrease in abundance at the end of embryogenesis, our efforts to simultaneously study the biology of these miRNAs and the mechanisms of miRNA decay has the potential to uncover regulatory modules that couple miRNA decay to developmental timing.

The NIH main campus is a vibrant and collaborative research environment boasting over four hundred research groups and an active postdoc community. Bethesda, Maryland is part of the Washington, D.C. metropolitan area, and the NIH main campus is easily accessible by the Washington, D.C. subway system.

Applicants must have completed a Ph.D. within the last three years. Expertise in molecular biology and strong verbal and written communication skills are required. Experience in either RNA biology or C. elegans research is desirable. International scientists and U.S. citizens are equally eligible for these fully-funded positions.

For more information, please see our website (bit.ly/mcjunkin). To apply, please send a cover letter describing which aspect of our research program you are interested to pursue, a CV, and contact information for three references to mcjunkin@nih.gov.

Thumbs up (No Ratings Yet)
Loading...

Categories: Jobs

An interview with Jayaraj Rajagopal

Posted by , on 5 October 2017

This interview by Aidan Maartens appeared in Development, Vol 144 Issue 19


 

Jayaraj (Jay) Rajagopal is a Principal Investigator at the Center for Regenerative Medicine at Massachusetts General Hospital and an Associate Professor of Medicine at Harvard Medical School. A Howard Hughes Medical Institute Faculty Scholar, his lab works on the development and regeneration of the lung. He uses stem cell and animal models to develop novel insights that hopefully will provide inspiration for therapies to help treat human lung disease. He was awarded the Dr Susan Lim Award for Outstanding Young Investigator at the 2017 International Society for Stem Cell Research (ISSCR) meeting in Boston (MA,USA), where we met him to talk about how a fish tank started a life-long fascination with the lung, the transition to running his own lab, and his optimism for the future of both basic stem cell research and its clinical translation.

 

 

You’re here in Boston to collect ISSCR’s Susan Lim Young Investigator award: what does the award mean to you?

It really was an incredible honour. I looked over the past recipients and the vast majority of them are either friends or people whose work I admire. Additionally, Susan Lim and her husband Deepak Sharma are just wonderful people – it was great to meet them, and especially their daughter who is interested in becoming a physician. Most of all, it represents a chance to be embedded in a rich community of scholarship that promotes education and younger researchers.

 

What got you interested in science in the first place?

That started very early for me: I was always intrigued by animals. I spent my summers in India as a child and when all my cousins were in school I’d be out on the farm, capturing animals and things like that. The other early influence was my father, who was a doctor and would talk with me about interesting cases. His perspective was great because he introduced these diseases as fascinating mysteries. For as long as I can remember, those two things – animals and medicine – were what I wanted to devote my professional life to.

 

How did you become interested in developmental biology and the development of the lung in particular?

I went to college at Harvard and studied molecular biology, and actually specifically avoided developmental biology! Having read The Eighth Day of Creation by Horace Freeland Judson, molecular biology seemed so exciting. I worked with Jack Szostak and Jenn Doudna at the time when self-splicing RNAs were new. We could synthesise the RNA molecules in vitro, put them in a solution and test their enzymatic activity with exquisite precision. The whole process was a lot of fun and appealingly very understandable. Then I went to medical school and loved the human biology and physiology, as well as being able to interact with and treat patients. But at some point I stepped back and asked myself: what do I love? I realised that, at heart, I like cells and tissues, and how they come together functionally to create a living animal, essentially exactly what I was fascinated by as a kid in a more mature guise. Developmental biology just seemed like the natural thing to do.

My interest in the lung also traces back to when I was young. I had a fish tank and even as a very young kid I was mesmerised by it: these animals could breathe underwater, but if you let your tank get dirty – like many kids do – many fish can also breathe air. In medical school I learned about the lung’s physiology, and how beautifully it works to bring oxygen to the bloodstream. When I was looking for a lab to join in Boston, there wasn’t anyone studying the lung in the way that I wanted to. Doug Melton was just getting interested in the pancreas, moving from his more basic work in the frog, and I thought that since the lung and the pancreas came from the same tube, I could help him figure out how to make a pancreas, and then once I was done with my training in his lab, I’d move a little anterior in the tube and make a lung. Doug thought it was a great idea, and we hit it off immediately. The best laid plans often change though. When induced pluripotent stem cells (iPSCs) came out, I immediately started working on making iPSCs into β-cells, and that got me hooked on stem cells. Doug really was a fantastic mentor to me, broadening my perspectives, encouraging me to explore the newest ideas and systems, while maintaining my fundamental interests.

 

What were your aims when you first started your lab?

As part of my interview at the Center for Regenerative Medicine at Massachusetts General Hospital I gave a chalk talk describing my ideas, but my actual research program ended up only very loosely related to that chalk talk. Essentially, I didn’t really know what I was going to do, except in very vague terms, and although I was empowered with new experimental tools and an understanding of the basis of experimentation, I was left with pretty much the same interests I had as a child: how do organs come to be?

When my lab started I was initially not so interested in the iPSC differentiation paradigms I had explored in Doug’s lab. Rather, I was enamoured of the developmental biology of the lung and particularly of tissue regeneration – it was so beautiful, and that’s what I focused on, primarily in the mouse because the biological tools were much more rigorous. Yet at the same time, I had always had this keen interest in human basic biology and in medicine – so I sort of put myself in Doug’s shoes again and eventually realised I would have to return to iPSCs. We reinvigorated that aspect of the lab, and then moved on to developing systems to grow adult lung stem cells, and I think we now have a way to use an actual human lung explant to do what I’ve always wanted to do: investigate the developmental biology of a regenerating human mini-organ.

 

What is it about the lung that is so fascinating as a developmental system?

For me one reason is evolution, which was another interest of mine since I was a kid. Back to my fishtank: it’s a mystery how fish came out of the water. How did the first lungs arise? The question of how it came about is fascinating. It’s also a fascinating organ in terms of its physiology, which I was introduced to during my medical studies. And something really appealing about the lung is that it is an organ par excellence for understanding regeneration. You have to breathe – which means there are physical forces and gas fluxes, and you inhale allergens, infections, toxins, dust and so on. All of the cardinal ways in which the environment could possibly perturb a tissue are captured in the lung. We’re really interested in how a perturbation in a tissue wrought by one of these injuries is resolved. I do often wonder whether there are some forms of simple equations that you could write to understand how cells come together to generate ensemble properties of tissues. It’s a very tall order, but there has got to be at least partially ordered ways of thinking about it, some ‘laws’ of regeneration.

And the lung is turning out to be a lot more complex than we previously thought. Doing single cell sequencing in collaboration with Aviv Regev we find two things: firstly, that there’s a whole new set of cells with interesting physiological properties; and secondly that many cells have specific immune signatures. The epithelium was considered to be pretty monotonous, and to interact with a panoply of weird different immune cells (you can see I’m not an immunologist!). Now it looks like there may be considerable crosstalk of particular epithelial cells types to particular types of immune cells. We also learned there are many subtypes of known cells, totally novel cells important for disease, and even new specialised structures in the airway.

For me it seemed like everything came together in the lung: aesthetics, evolution, developmental biology, the clinical aspect, and how the organ interacts with the environment. Somehow you just find your groove if you keep doing what you like, and the lung is a perfect lens with which to ask all the questions I’ve ever wanted to ask. I understand the developmental biology and some of the therapeutic issues, and then we are collaborating with people from other disciplines who look at the problem through different lenses. Some are computational biologists, physicists with new imaging techniques, immunologists, and I’m interested in collaborating with a whole suite of other biologists, including neuroscientists, evolutionary biologists and mathematical modellers. I don’t think that any single type of biologist is going to get close to sorting out the ‘laws’ of tissue behaviour unless they work together. It’s one of the most fun things in science: to head into totally new domains. It’s also a good way to make new friends! I get bored relatively easily and so like constantly hopping from one aspect of tissue biology to another: from evolution to signalling to force transduction to hypoxia. And I suspect many of these topics will become reincarnated in the lab as a new idea makes one of them seem appealing again. My tendency to dalliance works well for the postdocs as they can take their own projects with them to their own labs.

 

The lung is a perfect lens with which to ask all the questions I’ve ever wanted to ask

 

Many speakers at this meeting have emphasised the importance of developmental biology for stem cell research – how do you see the relationship between the two fields?

One way stem cell biology has helped developmental biology is that developmental biologists were so interested in embryogenesis, but tended not to think about the adult organism. Stem cell biology made developmental biologists think about the adult. The idea of stem cells is also just useful to convey enthusiasm, and that enthusiasm is incredibly important. Even in my own case, stem cells drew me into the problem of lung development and made me think about it differently. Stem cells are super interesting – but they are only one aspect of tissue function. There was a quote from Jean Rostand on the wall of Doug Melton’s lab which said ‘Theories come and go, but the frog remains’. I think this serves to remind us that there are tissues, organs and animals. Those exist, and all these different ways of doing science and naming cell functions are just different lenses with which to look at them, none of them complete in their own right and always evolving. As we analyse cells more deeply in the lung epithelium, we are finding that none is associated with a unitary specific function, but they all have many distinct activities. Stem cells aren’t just for replication and differentiation anymore. We have shown that they signal and I am sure they sense and perform necessary metabolic activities too.

It’s also important not to let the translational side eclipse everything else. The constant translational need, which is important, can become a drumbeat that moves you away from basic biology. Stem cells have this immediate connotation of being of use in a practical fashion, which is part of what makes them wonderful, but developmental biology has always come from the first principles of ‘I would just like to understand something’, and I think we cannot lose that because most of our truly game-changing ideas are a result of curiosity-driven basic biology.

Finally, stem cell research is an easy paradigm to communicate to patients and their families. It’s much harder to educate society at large about the interest and importance of basic biology. But I think we have to do that, especially with the modern political climate – there can’t be anything more important than to just explain to people why new knowledge is important.

 

So do you think the stem cell field as a whole is good at engaging with the public?

First of all, I think what the ISSCR does is spectacular, and I would in particular point out people like George Daley, Len Zon, David Scadden and Doug Melton, who are all great communicators, not just to the public at large, but also to our politicians. From my own perspective and background, I think we need to think about educating patients themselves, and to remember that they are vulnerable. I was a pulmonologist, and if I had a patient with, let’s say, idiopathic pulmonary fibrosis, they would walk into the office short of breath. More or less the one thing I could do for them was to give them oxygen – that is where the treatment ended. So you can imagine my inbox was full of messages from people who couldn’t get a new functioning lung with a lung transplant. These patients all wanted ‘stem cells’. I’m usually very straightforward in my response to them: although I empathise with what they have to go through because I’ve seen it first hand, I tell them that currently, there are no stem cell therapies for the lung, and that I would be very careful because there are a lot of people squirting stem cells into people without the proper science. But at the same time I try to give them the optimism of research, because I really do believe in it, and I am only getting more optimistic about it these days. I really think there is going to be a renaissance in terms of therapies produced through iPSCs and organoid models, and I try to fill patients with that kind of optimism. Unfortunately, you can’t give patients a timetable when they are desperate for a cure, but I can honestly say the research keeps moving faster and faster than I could ever have imagined.

At one point in my career, we wanted to make iPSCs from cystic fibrosis patients so that we could model the disease. I talked to some of my clinician friends, and they agreed to ask some of their patients to contribute, and the result was unbelievable – within a couple of weeks, we were turning people away. It’s overwhelming to see that kind of enthusiasm from patients: even if you tell them that this donation is very unlikely to help them personally, they still want to contribute. It’s also reciprocal: one of my graduate students working on a cystic fibrosis-related project asked me if he could meet a patient. My clinical friends again had a patient lined up to meet him before you could imagine it, and that patient spoke to my laboratory. It just blew them away and made their research so much more meaningful. If you are a PhD scientist working on a disease at the bench, you’re missing something. If you’ve come to meet patients, when an experiment fails 90 times, there is another reason you’re repeating it – it’s not just that you want the answer, but there’s a person that needs your help.

 

Being a PI was just intrinsically so much more fun for me than being a postdoc

 

When you started your lab, what was the transition to being a PI like?

I have to say that I found my post-doctoral fellowship very hard. I came from clinical medicine, and was used to knowing what to do – even if you couldn’t save every patient, you knew you could do your job well, and in a well-defined way. In science, it didn’t work that way and, quite frankly, it took me a long time to learn how to fail, and to appreciate the importance of problem solving. I am actually one of those scientists that did not love bench work, but rather I preferred to look at and think about data, talk to colleagues about new ideas and dream up future experiments. I had also always known, since I had been a Chief Resident in Internal Medicine at Massachusetts General Hospital, that mentoring was my absolute favourite thing. So it turned out that being a PI was just intrinsically so much more fun for me than being a postdoc, for almost every single reason. Again, I’d found my groove – being a laboratory head is the job I was ‘supposed’ to do, and it has only gotten better and better and better. I can’t imagine a job that is more fun, and I think the core value I treasure about it, perhaps even more than the study of living things, is the freedom it provides me.

One great thing about lung science for me is that, unlike haematopoiesis, neuroscience or immunology, it is so understudied, and so it’s just a great place for me to train young scientists. I’m so pleased to say that the first four scientists to have graduated from my lab all have their own labs. I don’t think I’ll ever have a very big lab – I like to put a lot of energy into every single postdoc and student, and hopefully have all of them leave and still love biology, no matter what they decide to do. That said, I’m hoping every single one will have their own laboratory if that is what appeals to them. Also, thanks to the Harvard Stem Cell Institute and my relationship to the undergraduate Stem Cell and Regenerative Biology Department at Harvard University, we always have undergraduates in the lab. It’s just fantastic to have people at every single stage of their education and career. Having undergraduates in my lab also means my postdocs and graduate students have a mentee, which is also a crucial part of growing as a scientist.

 

Do you have any advice for someone thinking about a scientific career today?

There have been editorials written by very prominent scientists that have said that we are training too many PhDs; I completely disagree with this! If anything I would say we are training too few, because while you can look at a PhD as a means towards one particular end, you could also look at it as a pure form of education that trains you to think and problem solve, and also to communicate in various ways. In some sense it’s a liberal arts education in terms of problem solving. But if you gravitated towards writing you could become a wonderful editor, if you gravitated towards ethics, politics or law, you can go into those roles. You can go into clinical medicine: a doctor who understands science is very valuable, just like a scientist who understands medicine. I remember in my own time, it used to be considered wrong to go to a company; now there are brilliant scientists who want to go to a company from day one. I love being a PI, and it’s a path I want to encourage but I’d like to see my young people in diverse spheres of human activity that captivate their imagination. The more people we have doing different things, but bound by a respect for scientific inquiry, the better.

I would say to a young person: explore and try to figure out what you love, and don’t worry too much about exactly where you’ll be 20 years from now because, in my view, no one really knows. Life is an experiment with no controls – at some level we’ll never know whether we’ve taken the right path – but if you’re constantly doing something you’re excited about, work becomes play. If you can live a life where work is always play, you have sealed the deal professionally. On top of that, you have to think about work-life balance – different paths have different constraints, and it’s important to talk to people who have lives that you’d want to emulate at work and also at home. Similarly with money: different people have different thresholds concerning what they are comfortable earning, and it’s important to think about this (but money can’t buy you love). I’d also advise people to ask for advice and help from people they respect. Mentors who listen and empathise, and who have a solid sense for your abilities can be invaluable for you as they were for me. I’ve found many people believed in my ultimate success and that was enormously encouraging at times when I did not think I could rise to the level of my own scientific bar.

 

Is there anything that Development readers would be surprised to find out about you?

Well the things I love outside of the lab are music, reading, the arts, travel and my family. I guess they’re all about exploration, and that might be the common theme. It’s a pretty interesting life to be able to combine all of these things.

Perhaps the other thing is that I’ve never left Boston since coming here for college, where in fact I met my wife in my freshman year! I’ve always found Boston to be supportive – people often think of it as an intense and competitive environment, but I’ve found it to be completely the opposite. Whenever I’ve asked for help, I’ve gotten it!

 

Thumbs up (1 votes)
Loading...

Tags: , ,
Categories: Interview

DORA Community Manager

Posted by , on 4 October 2017

Closing Date: 15 March 2021

 

 

The DORA Community Manager position is an opportunity for a Ph.D. or Master level fellow to gain experience in scholarly publishing and policy in Washington, DC. The DORA Community Manager will be headquartered at the American Society for Cell Biology (ASCB), which is located in Bethesda, MD. This position will report to the Director of Public Policy and is a 24 month assignment.

 

Essential Functions

 

Documenting best practices in Research Assessment

  • Research and document examples of best practice of research assessment for different situations from a range of organizations, in particular DORA signatories.

 

Website and outreach

  • Regularly blog, post to social media and send newsletters to signatories about issues related to DORA and progress on documenting best practices in order to keep awareness of this issue high.
  • Work with relevant staff to maintain DORA website and ensure that it is a regularly updated source of valuable information.

 

Management of DORA signatories and data

  • Assure the quality of the current data on institutional signers of DORA and recruit additional institutions, for example to improve the international coverage.
  • Work with the Steering Committee to target and recruit new institutional subscribers.

 

Committee Management and Strategic Partnerships

  • Develop strategic partnerships with groups who are working in highly related areas and can help to amplify the DORA message or assist in its activities.
  • Provide monthly updates to the Core Steering Committee.
  • Support the activity of the Core Steering Committee including creation of agendas for quarterly meetings.
  • Liaise with individual members of the Core Steering Committee as necessary and with staff who are involved DORA nodes in other parts of the world.

 

Competencies

 

  1. Technical Capability in communications, data management, and analytics
  2. Strategic Thinking
  3. Communication Proficiency
  4. Project Management
  5. Attention to detail
  6. Creative problem-solving ability

Required Education and Experience

 

  • Master’s or Ph.D. in the sciences preferred
  • Knowledge of scholarly publishing, assessment of research
  • Strong written and verbal communication including the use of social media

 

 

FOR IMMEDIATE CONSIDERATION:

Please e-mail your resume and one page cover letter with salary requirements to jobs@ascb.org

Thumbs up (No Ratings Yet)
Loading...

Categories: Jobs

The people behind the papers – Simon Lane & Keith Jones

Posted by , on 4 October 2017

Checkpoints ensure that mouse oocytes with DNA damage arrest in meiosis I, preventing non-viable embryo formation, however the mechanisms which activate this checkpoint have so far eluded researchers. This week we feature a paper published in the latest issue of Development that reveals that the unique ability of mouse oocytes to sense DNA damage by rapid kinetochore checkpoint activation. First author Simon Lane and his PI Keith Jones of the University of Southampton, told us more.

 

Keith Jones and Simon Lane

 

Keith, please can you give us your scientific biography and the main questions your lab is trying to answer?

KJ I am Head of Biological Sciences, and Chair of Cell Biology at the University of Southampton. In the mid 1990s I worked at the Medical Research Council Experimental Embryology & Teratology Unit in London, examining the way in which sperm-driven changes in intracellular calcium at fertilization were regulated and how they affected embryo quality, helping to establish a link between early events of fertilization and long term embryo quality.

Between 1998 and 2008 I held an academic position in the Institute for Cell and Molecular Biosciences at the University of Newcastle-upon Tyne, UK. My lab has helped develop the use of Fluorescent Proteins to study the process of meiosis in real-time. This approach led to recent developments in the understanding of how the meiotic divisions are regulated.  In 2008, until 2012, I moved to University of Newcastle, Australia, where Simon joined me as a PhD student. In 2012 I moved back to the UK and Simon followed me, then as a postdoc having successfully defended his thesis.

My lab is focused on understanding how the oocyte makes the transition in meiosis from a mature egg.

 

Simon, how did you come to join the Jones lab?

SL After receiving an interesting lecture on fertilisation in ascidian eggs I applied for a summer placement in the cell biology labs in Newcastle University. There I met Keith who was about to move his lab to Australia and was recruiting PhD students. I didn’t hesitate at the opportunity to do a PhD in a subject that was very interesting and in such an exciting part of the world!

 

Can you give us a brief summary of why you decided to ask the questions in your paper and the previous research that led you to this story?

KJ Along with the John Carroll lab (then UCL, now Monash) we made the original discovery of the ability of oocytes to arrest in meiosis I a few years ago.

The current work is an extension of that initial study. The first study was all about reporting the phenomenon. The present one, published in Development, is a more detailed investigation of the mechanism by which arrest is achieved.

 

Can you give us the key results of the paper in a paragraph?

KJ In a nutshell it shows that oocytes have a profound ability to arrest in meiosis I in response to DNA damage, and that the mechanism by which this achieved is unusual. It’s a process that involves the kinetochore, rather than the sites of DNA damage, and it doesn’t involve the usual DDR kinases ATM and ATR. We also show that the response is specific to the first meiotic division, as it is absent in mature eggs.

 

Imagining the kinetochores, from Figure 6, Jones, et al. 2017

 

You suggest three models for MI oocyte sensitivity to DNA damage, how might you proceed to test your preferred model?

KJ The paper shows the response specific to the first meiotic division. We are therefore pursuing the role of various proteins known to play specific functions during the first but not the second meiotic division.

 

Possible models to explain meiosis I-specific arrest, from Figure 9, Jones, et al. 2017

In the paper you talk about potential implications for human oocytes: how well do you think the mouse model translates and do you have any plans to test this research in human cells?

KJ We already know that follicular fluid collected from the ovaries of women who have endometriosis is able to cause arrest of mouse oocytes during in vitro maturation. The mechanism we believe is that ROS levels are higher in endometriosis, a phenomenon associated with inflammation, and the increased free radicals have the ability to damage DNA.

 

When doing the research, did you have any particular result or eureka moment that has stuck with you?

SL I like the feeling when you are working late to complete an experiment but then you see something new and interesting and you think to yourself, I might just be the first person who has ever seen this. The experiment where the Mad1 response to DNA damage is completely different between oocytes and eggs was like that.

 

DNA-damaged mature eggs can complete meiosis II, from Figure 8, Jones et al. 2017

 

And on the flipside: any moments of frustration or despair?

SL There are many of these moments (more frustration than despair), it’s a part of the process I guess. So many things have to come together at once to get each experiment working so it keeps you constantly on your toes!

 

What are your career plans following this work?

SL I’m currently in the process of applying for fellowships.

 

And what is next for the Jones lab?

KJ  I’d really like to figure out how the kinetochore function in meiosis. This seems a little dull at first, yet the structure of the chromosomes and how the segregate in meiosis I are unique, with co-segregation of sister kinetochores happening only in this division. Understanding how this co-segregation is achieved and how the meiotic spindle microtubules interact with the fused sister kinetochores are probably the most fundamental unknowns in meiosis.

 

Finally, what do you two like to do when you are not in the lab?

KJ My partner likes to tell me that my work is my only hobby! I think, although am not certain, this is a windup. I enjoy walking, good wines (I have been really surprised at the excellent sparkling wines made in Hampshire- next to Southampton), cooking, and BBC4 podcasts-take these in any combination. My work takes me round the world so I consequently do enjoy travel.

SL I keep fit with boot-camp style training and also like to experiment with 3D printing and electronics projects.


Simon I. Lane, Stephanie L. Morgan, Tianyu Wu, Josie K. Collins, Julie A. Merriman, Elias Ellnati, James M. Turner and Keith T. Jones. 2017. DNA damage induces a kinetochore-based ATM/ATR-independent SAC arrest unique to the first meiotic division in mouse oocytes. Development. Volume 144, Issue 19, p3475-3486.

This is #29 in our interview series. Browse the archive here

Thumbs up (1 votes)
Loading...

Tags: , , , ,
Categories: Interview

Postdoctoral Position in Cellular Reprogramming and Hematopoiesis

Posted by , on 4 October 2017

Closing Date: 15 March 2021

The Reprogramming and Hematopoiesis lab is currently seeking a highly motivated postdoctoral fellow!

Reprogramming and Hematopoiesis lab

Cellular reprogramming can be achieved experimentally in different ways, including nuclear transfer, cell fusion or expression of transcription factors. We aim to uncover how hematopoietic stem cell and effector cell identity is established employing cellular reprogramming logic. Ultimately our work may allow the generation of patient-specific hematopoietic cells for regenerative medicine and immunotherapy. To explore these aims, we use a variety of approaches, including cellular reprogramming through gene transduction (Pereira et al, Cell Stem Cell, 2013) and single cell gene expression profiling during embryonic development (Pereira et al, Developmental Cell, 2016). Hematopoiesis is a core area of research at the Medical Faculty at Lund University. Within this broader research area the Division of Molecular Medicine and Gene therapy harbors an ensemble of international research groups with a focus on understanding both normal and malignant hematopoiesis and to develop new strategies for therapeutic intervention. Our lab is generously funded by the Wallenberg Centre for Molecular Medicine and the Knut and Alice Wallenberg Foundation.

Candidate Profile

The candidate should be an enthusiastic and motivated scientist willing to join a young international research group in a highly dynamic and multidisciplinary environment (with English as main language). Candidates with a passion for cell identity and epigenetics as well as immunology and/or hematopoiesis who recently completed their PhD thesis or currently finishing up are encouraged to apply. The successful candidate will join a research program at the interface between the fields of cellular reprogramming and stem cells, hematopoiesis and oncoimmunology. Excellent verbal and written communication skills in English are required.

Research at Lund University

Lund University is Scandinavia’s largest institution for education and research and consistently ranks among the world’s top 100 universities. The Lund Stem Cell Center hosts 15 research groups in experimental hematology and is one of Europe’s most prominent in the field of hematopoietic research. This environment has all facilities and equipment essential for the project including an outstanding animal facility, technical platforms for flow cytometry and cell sorting, a human ES/iPS core facility, viral vector technology and single cell genomics facility. This creates a very interactive environment with weekly seminars and annual retreats for students, postdocs and PIs.

Experimental Approaches

Key approaches will include flow cytometry, high-content automated image acquisition and analysis, single cell gene expression and chromatin profiling, cellular transplantation, Crispr/Cas9 and small molecule screening and the generation and characterization of new mouse models.

Start of Position and Application Deadline

The position start date is flexible from October 2017. Application deadline: 31st October 2017.

How to apply

Please send a letter of motivation, your curriculum vitae, and the contacts for three references to:

Assistant Professor Carlos-Filipe Pereira
Contact: filipe.pereira@med.lu.se

 

References

Pereira, C.F.**; Chang, B.; Gomes, A.; Bernitz, B.; Papatsenko, D.; Niu, X.; Swiers, G.; Azzoni, E.; Brujin M.F.T.R.; Schaniel, C.; Lemischka, I.R.; Moore, K.A. Hematopoietic Reprogramming In Vitro Informs In Vivo Identification of Hemogenic Precursors to Definitive Hematopoietic Stem Cells. Developmental Cell 2016, 36 (5), 525-39. **corresponding author.

 

Pereira, C. F. **; Chang, B.; Qiu, J.; Niu, X.; Papatsenko, D.; Hendry, C. E.; Clark, N. R.; Nomura-Kitabayashi, A.; Kovacic, J. C.; Ma’ayan, A.; Schaniel, C.; Lemischka, I. R.; Moore, K., Induction of a hemogenic program in mouse fibroblasts. Cell Stem Cell 2013, 13 (2), 205-18. **corresponding author.

Thumbs up (No Ratings Yet)
Loading...

Categories: Jobs

Worm study reveals role of stem cells in cancer

Posted by , on 3 October 2017

A new study carried out by the University of Oxford has used flat worms to look at the role of migrating stem cells in cancer


Researchers from the Aboobaker lab in the Department of Zoology used the worms (planarians) which are known for their ability to regenerate their tissues and organs repeatedly. This process is enabled by their stem cells, which constantly divide to make new cells.

Cell migration – or the movement of cells from one part of the body to another – is a key function of cells in our bodies. New stem cells are constantly required to maintain tissue and organs functions, and they are expected to migrate to where they are needed. However, control of these movements can fail, and cancers can form when these cells migrate to places they aren’t supposed to be.

By understanding how stem cells are programmed to move, what activates them and how they follow a correct path, researchers may be able to design new treatments for cancer.

‘We already knew that these worm stem cells have a lot in common with our own stem cells, but we knew nothing about how they migrate and if this process relates to how our cells migrate,’ says Dr Prasad Abnave, first author of the study, published in Development.

 

 

‘We wanted to establish if the same mechanisms had been evolutionary conserved or not, we hoped that they would be, as this would make an excellent model for studying all aspects of stem cell migration.’

However, before the team could start working with the worms, they had to overcome a small problem. ‘Perhaps a little counterintuitively, the sheer abundance of stem cells in planarians makes it difficult to study migration,’ said Professor Aziz Aboobaker.

‘In order to trace the movement of cells you need to create a field for them to move into so you can be sure of the direction and speed at which their moving, but if the cells you are interested in are already everywhere that is difficult to do.’

Luckily the team were able to draw on over 100 years of previous work. In one particular experiment that used x-rays to kill planarian stem cells, it was found that the animals survived the treatment if part of the worm was kept under a lead shield, as ‘presumably the stem cells under the lead shield migrate to the rest of the animal and everything is fine.’ said Abnave.

With the help of Dr Mark Hill at Oxford’s Department of Oncology the group were able to design an apparatus that allowed them to use X-rays to leave behind a thin strip of stem cells. These cells could then be observed as they migrated through the rest of the organism to where the original stem cells had been killed.

‘This collaboration gave us a great opportunity to apply previous experience gained in studying cancer cells to a study involving cells in a whole organism. It will provide a useful tool to improve our understanding of stem cells, and their potential role in cancer,’ said Mark.

‘It sounds simple, but it took a long time to design an apparatus and techniques with which we could study many worms at once. That was key in being able to study how migration was controlled and for performing high quality experiments that could really generate reproducible results,’ said Aboobaker.

Professor Gillies McKenna, the Director of the CRUK / MRC Institute for Radiation Oncology and Biology commented: ‘This project is an example of why Oxford is such a rewarding place to do research. People from different departments and disciplines bringing their expertise together to tackle a problem neither could do alone but together shedding new light on both fundamental biology and also on cancer.’

By studying how the worms respond to injury, the team found that stem cells migrated very precisely to the affected area. However in the absence of damaged tissue the cells sat still and did not migrate.

Using a technique called RNA interference the team were then able to remove the function of regulatory genes already known to be important in cell migration (and to play a role in human cancers) and found that they were all also required for migration of planarians stem cells. These genes included proteins known as transcription factors that are important because they act as ON/OFF switches for hundreds of other genes.

‘This was a very satisfying result as it confirmed our suspicion that our simple worms will be very useful for understanding stem cell migration, now we have proven the system we can look intensely for new mechanisms that control or interact with cell migration and have a real expectation that we find will also be true for our migrating cells” said Abnave. One advantage of our worms is that they are easy to work with and we can make rapid progress.’

Next the team hopes to look for new genes that control stem cell migration using the system they have developed.

Thumbs up (1 votes)
Loading...

Categories: Highlights, Research

September in preprints

Posted by , on 3 October 2017

Our latest monthly trawl for developmental biology (and other cool) preprints. See last year’s introductory post for background, and let us know if we missed anything.


 

This month features butterfly eyespots, brain development in vivo and in silico, lots on cell commitment in embryos and dishes, a diverse selection of modelling preprints, and, right at the end in our ‘Why not…’ section, some algorithmic science art inspired by sand-bubbler crabs!

The preprints were hosted on bioRxivPeerJ, arXiv and Wellcome Open Research. Use these links to get to the section you want:

 

Developmental biology

Patterning & signalling

Morphogenesis & mechanics

Genes & genomes

Stem cells, regeneration & disease modelling

Evo-devo & evo
Cell biology
Modelling
Tools & resources

| Imaging etc.

| Genome tools

Research practice
Why not…

 

Developmental biology

| Patterning & signalling

 

Cultured blastocysts from Miller, et al.’s preprint

 

Transcriptional control by Sall4 in blastocysts facilitates lineage commitment of inner cell mass cells. Anzy Miller, Sarah Gharbi, Charles Etienne-Dumeau, Ryuichi Nishinakamura, Brian Hendrich

 

Dephosphorylation of the NPR2 guanylyl cyclase contributes to inhibition of bone growth by fibroblast growth factor. Leia C. Shuhaibar, Jerid W. Robinson, Ninna P. Shuhaibar, Jeremy R. Egbert, Giulia Vigone, Valentina Baena, Deborah Kaback, Siu-Pok Yee, Robert Feil, Melanie C. Fisher, Caroline N. Dealy, Lincoln R. Potter, Laurinda A. Jaffe

 

Reconstruction of developmental landscapes by optimal-transport analysis of single-cell gene expression sheds light on cellular reprogramming.  Geoffrey Schiebinger, Jian Shu, Marcin Tabaka, Brian Cleary, Vidya Subramanian, Aryeh Solomon, Siyan Liu, Stacie Lin, Peter Berube, Lia Lee, Jenny Chen, Justin Brumbaugh, Philippe Rigollet, Konrad Hochedlinger, Rudolf Jaenisch, Aviv Regev, Eric Lander

 

MCAM contributes to the establishment of cell autonomous polarity in myogenic and chondrogenic differentiation. Artal Moreno-Fortuny, Laricia Bragg, Giulio Cossu, Urmas Roostalu

 

Early worm embryos from Liro, et al.’s preprint

 

The kinases PIG-1 and PAR-1 act in redundant pathways to regulate asymmetric division in the EMS blastomere of C. elegans. Malgorzata J. Liro, Diane G. Morton, Lesilee S. Rose

 

In vivo relevance of intercellular calcium signaling in Drosophila wing development. Qinfeng Wu, Pavel Aleksandrovich Brodskiy, Francisco Javier Huizar, Jamison John Jangula, Cody Narciso, Megan Kathleen Levis, Teresa Brito-Robinson, Jeremiah J. Zartman

 

Intercellular calcium signaling is regulated by morphogens during Drosophila wing development. Pavel A. Brodskiy, Qinfeng Wu, Francisco J. Huizar, Dharsan K. Soundarrajan, Cody Narciso, Megan Levis, Ninfamaria Arredondo-Walsh, Jianxu Chen, Peixian Liang, Danny Z. Chen, Jeremiah James Zartman

 

The hominoid-specific gene DSCR4 is involved in regulation of human leukocyte migration. Morteza Mahmoudi Saber, Marziyeh Karimiavargani, Nilmini Hettiarachchi, Michiaki Hamada, Takanori Uzawa, Yoshihiro Ito, Naruya Saitou

 

Ldb1 and Rnf12-dependent regulation of Lhx2 controls the relative balance between neurogenesis and gliogenesis in retina. Jimmy de Melo, Anand Venkataraman, Cristina Zibetti, Brian S. Clark, Seth Blackshaw

 

Tracking microvillous sensory neuron origins, from Aguillon, et al.’s preprint

 

Cell-type heterogeneity in the zebrafish olfactory placode is generated from progenitors within preplacodal ectoderm. Raphaël Aguillon, Julie Batut, Pascale Dufourcq, Romain Madelaine, Arul Subramanian, Thomas F. Schilling, Patrick Blader

 

Developmental diversification of cortical inhibitory interneurons. Christian Mayer,Christoph Hafemeister, Rachel C Bandler, Robert Machold, Kathryn Allaway, Xavier Jaglin, Renata Batista Brito, Andrew Butler, Gord Fishell, Rahul Satija

 

Modulation of apoptosis controls inhibitory interneuron number in the cortex. Myrto Denaxa, Guilherme Neves, Adam Rabinowitz, Sarah Kemlo, Petros Liodis, Juan Burrone, Vassilis Pachnis

 

Paupar LncRNA Promotes KAP1 Dependent Chromatin Changes And Regulates Subventricular Zone Neurogenesis. Ioanna Pavlaki, Farah Alammari, Bin Sun, Neil Clark, Tamara Sirey, Sheena Lee, Dan J. Woodcock, Chris P. Ponting, Francis G. Szele, Keith W. Vance

 

Single-cell transcriptomic profiling of progenitors of the oligodendrocyte lineage reveals transcriptional convergence during development. Sueli Marques, Darya Vanichkina, David van Bruggen, Elisa Floriddia, Hermany Munguba, Leif Varemo, Stefania Giacomello, Ana Mendanha Falcao, Mandy Meijer, S Samudyata, Simone Codeluppi, Asa Bjorklund, Sten Linnarsson, Jens Hjerling-Leffler, Ryan Taft, Goncalo Castelo-Branco

 

Embryonic and postnatal neurogenesis produce functionally distinct subclasses of dopaminergic neuron.Elisa Galliano, Eleonora Franzoni, Marine Breton, Annisa N. Chand, Darren J. Byrne, Venkatesh N. Murthy, Matthew S. Grubb

 

ELMOD1 stimulates ARF6-GTP hydrolysis to stabilize apical structures in developing vestibular hair cells. Jocelyn F Krey, Rachel A Dumont, Philip A Wilmarth, Larry L David, Kenneth R Johnson, Peter G Barr-Gillespie

 

Tracking mouse gonad development in mice, from Stevant, et al.’s preprint

 

Deciphering cell lineage specification during male sex determination with single-cell RNA sequencing. Isabelle Stevant, Yasmine Neirijnck, Christelle Borel, Jessica Escoffier, Lee B Smith, Stylianos E Antonarakis, Emmanouil T Dermitzakis, Serge Nef

 

Tissue specific auxin biosynthesis regulates leaf vein patterning. Irina Kneuper, William David Teale, Jonathan Edward Dawson, Ryuji Tsuggeki, Klaus Palme, Eleni Katifori, Franck Anicet Ditengou

 

Cross-species functional diversity within the PIN auxin efflux protein family. Devin Lee O’Connor, Samuel Elton, Fabrizio Ticchiarelli, Mon Mandy Hsia, John Vogel, Ottoline Leyser

 

The ERA-related GTPase AtERG2 associated with mitochondria 18S RNA is essential for early embryo development in Arabidopsis. Pengyu Cheng, Hongjuan Li, Linlin Yuan, Huiyong Li, Lele Xi, Junjie Zhang, Jin Liu, Yingdian Wang, Heping Zhao, Huixin Zhao, Shengcheng Han

 

Karrikin-sensing protein KAI2 is a new player in regulating root growth patterns. Stephanie M. Swarbreck, Yannick Guerringue, Elsa Matthus, Fiona J. C. Jamieson, Julia M. Davies

 

The CLAVATA receptor FASCIATED EAR2 responds to different CLE peptides by signaling through different downstream effectors. Byoung Il Je, Fang Xu, Qingyu Wu, Lei Liu, Robert Meeley, David Jackson

 

Mouse brain vasculature from Di Giovanna, et al.’s preprint

 

Whole-brain vasculature reconstruction at the single capillary level. Antonino Paolo Di Giovanna, Alessandro Tibo, Ludovico Silvestri, Marie Caroline Muellenbroich, Irene Costantini, Anna Letizia Allegra Mascaro, Leonardo Sacconi, Paolo Frasconi, Francesco Saverio Pavone

 

Conserved Neural Circuit Structure Across Drosophila Larval Development Revealed By Comparative Connectomics. Stephan Gerhard, Ingrid Andrade, Richard D. Fetter, Albert Cardona, Casey M. Schneider-Mizell

 

Worm oocyte development from Lee, et al.’s preprint

 

CYK-4 functions independently of its centralspindlin partner ZEN-4 to cellularize oocytes in germline syncytia. Kian-Yong Lee, Rebecca A. Green, Edgar Gutierrez, J. Sebastian Gomez-Cavazos, Irina Kolotuev, Shaohe Wang, Arshad Desai, Alex Groisman, Karen Oegema

 

Bacterial Colonization Stimulates A Complex Physiological Response In The Immature Human Intestinal Epithelium. David R. Hill, Sha Huang, Melinda S. Nagy, Veda K. Yadagiri, Courtney Fields, Dishari Mukherjee, Brooke Bons, Priya H. Dedhia, Alana M. Chin, Yu-Hwai Tsai, Shrikar Thodla, Thomas M. Schmidt, Seth Walk, Vincent B. Young, Jason R. Spence

 

C. elegans DBL-1/BMP Regulates Lipid Accumulation via Interaction with Insulin Signaling. James Clark, Michael Meade, Gehan Ranepura, David H Hall, Cathy Savage-Dunn

 

 

| Morphogenesis & mechanics

Motility-gradient induced elongation of the vertebrate embryo. Ido Regev, Karine Guevorkian, Olivier Pourquie, L. Mahadevan

 

Drosophila egg chambers from Sallak, et al.’s preprint

 

Src42A required for collective border cell migration in vivo. Yasmin Sallak, Alba Yurani Torres, Hongyan Yin, Denise Montell

 

A “molecular guillotine” reveals an interphase function of Kinesin-5. Zhiyi Lv, Jan Rosenbaum, Timo Aspelmeier, Jorg Grosshans

 

Drosophila beta-Tubulin 97EF is upregulated at low temperature and stabilizes microtubules. Faina Myachina, Fritz Bosshardt, Johannes Bischof, Moritz Kirschmann, Christian F. Lehner

 

Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction. Laetitia Weinhard, Urte Neniskyte, Giulia di Bartolomei, Giulia Bolasco, Pedro Machado, Nicole Schieber, Melanie Exiga, Auguste Vadisiute, Angelo Raggioli, Andreas Schertel, Yannick Schwab, Cornelius T. Gross

 

Centrosomes in the worm embryo, from Medley, et al.’s preprint

 

APC/CFZR-1 Controls SAS-5 Levels to Regulate Centrosome Duplication in Caenorhabditis elegans. Jeffrey C. Medley, Lauren E. DeMeyer, Megan M. Kabara, Mi Hye Song

 

Re-evaluating functional landscape of the cardiovascular system during development. Norio Takada, Madoka Omae, Fumihiko Sagawa, Neil Chi, Satsuki Endo, Satoshi Kozawa, Thomas N Sato

 

Role of midbody remnant in meiosis II creating tethered polar bodies. Alex McDougall, Celine Hebras, Gerard Pruliere, David Burgess, Vlad Costache, Remi Dumollard, Janet Chenevert

 

Non-Elastic Remodeling of the 3D Extracellular Matrix by Cell-Generated Forces. Andrea Malandrino, Michael Mak, Xavier Trepat, Roger D. Kamm

 

Depth Dependent Nanomechanical Analysis of Extracellular Matrix in Multicell Spheroids. Varun Vyas, Melani Solomon, Gerard G. M. D’Souza, Bryan D. Huey

 

 

| Genes & genomes

The HoxD Cluster is a Dynamic and Resilient TAD Boundary Controling the Segregation of Antagonistic Regulatory Landscapes. Eddie Rodriguez-Carballo, Lucille Lopez-Delisle, Ye Zhan, Pierre Fabre, Leonardo Beccari, Imane El-Idrissi, Thi Hahn Nguyen Huynh, Hakan Ozadam, Job Dekker, Denis Duboule

 

Spatially uniform establishment of chromatin accessibility in the early Drosophila embryo. Jenna E. Haines, Michael B. Eisen

 

dmrad51/spnA mutant exhibit defects during somatic stages of developmental and show enhanced genomic damage, cell death and low temperature sensitivity. Chaitali Khan, Sonia Muliyil, Champakali Ayyub, Basuthkar J. Rao

 

Chromatin organization changes during the establishment and maintenance of the postmitotic state. Yiqin Ma, Laura Buttitta

 

 

Rendered OPT hearts, from Sun, et al.’s preprint

 

Cardiac enriched BAF chromatin remodeling complex subunit Baf60c regulates gene expression programs essential for heart development and function. Xin Sun, Swetansu Hota, Yu-Qing Zhou, Stefanie Novak, Dario Miguel-Perez, Danos Christodoulou, Christine Seidman, Jonathan Seidman, Carol Gregorio, Mark Henkelman, Janet Rossant, Benoit Bruneau

 

Nkx2.5-dependent alterations of the embryonic heart DNA methylome identify novel cis-regulatory elements in cardiac development. Bushra Gorsi, Timothy Mosbruger, Megan Smith, Jonathon Hill, H. Joseph Yost

 

Gene neighbourhood integrity disrupted by CTCF loss in vivo. Dominic Lee, Wilson Tan, George Anene, Peter Li, Tuan Danh, Zenia Tiang, Shi Ling Ng, Motakis Efthymios, Matias Autio, Jianming Jiang, Melissa Fullwood, Shyam Prabhakar, Roger Foo

 

Nonparametric Bayesian inference of transcriptional branching and recombination identifies regulators of early human germ cell development. Christopher Andrew Penfold, Anastasiya Sybirna, John Reid, Yun Huang, Lorenz Wernisch, Zoubin Ghahramani, Murray Grant, M. Azim Surani

 

The FACT complex is required for DNA demethylation at heterochromatin during reproduction in Arabidopsis. Jennifer Frost, M. Yvonne Kim, Guen-Tae Park, Ping-Hung Hsieh, Miyuki Nakamura, Samuel Lin, Hyunjin Yoo, Jaemyung Choi, Yoko Ikeda, Tetsu Kinoshita, Yeonhee Choi, Daniel Zilberman, Robert L. Fischer

 

Genetic Identification of Novel Separase regulators in Caenorhabditis elegans. Michael Melesse, Dillon E. Sloan, Joseph T. Benthal, Quincey Caylor, Krishen Gosine, Xiaofei Bai, Joshua N. Bembenek

 

Pleiotropy in enhancer function is encoded through diverse genetic architectures. Ella Preger-Ben Noon, Gonzalo Sabarís, Daniela Ortiz, Jonathan Sager, Anna Liebowitz, David L. Stern, Nicolas Frankel

 

Small RNAs are trafficked from the epididymis to developing mammalian sperm. Upasna Sharma, Fengyun Sun, Brian Reichholf, Veronika Herzog, Stefan Ameres, Oliver Rando

 

Ploidy changes, centrosomes and spindles from Yaguchi, et al.’s preprint

 

Uncoordinated centrosome duplication cycle underlies the instability of non-diploid states in mammalian somatic cells. Kan Yaguchi, Ryo Matsui, Takahiro Yamamoto, Yuki Tsukada, Atsuko Shibanuma, Keiko Kamimura, Toshiaki Koda, Ryota Uehara

 

Frequent lack of repressive capacity of promoter DNA methylation identified through genome-wide epigenomic manipulation. Ethan Edward Ford, Matthew R. Grimmer, Sabine Stolzenburg, Ozren Bogdanovic, Alex de Mendoza, Peggy J. Farnham, Pilar Blancafort, Ryan Lister

 

Arabidopsis in different temperatures from Tasset, et al.’s preprint

 

POWERDRESS-mediated histone deacetylation is essential for thermomorphogenesis in Arabidopsis thaliana. Celine Tasset, Avilash Singh Yadav, Sridevi Sureshkumar, Rupali Singh, Lennard van der Woude, Maxim Nekrasov, David Tremethick, Martijn van Zanten, Sureshkumar Balasubramanian

 

Telomere repeats induce domains of H3K27 methylation in Neurospora. Kirsty Jamieson, Kevin J McNaught, Tereza Ormsby, Neena A. Leggett, Shinji Honda, Eric U Selker

 

Functional redundancy of variant and canonical histone H3 lysine 9 modification in Drosophila. Taylor J. R. Penke, Daniel J. McKay, Brian D. Strahl, A. Gregory Matera, Robert J. Duronio

 

NF90/ILF3 is a transcription factor that promotes proliferation over differentiation by hierarchical regulation in K562 erythroleukemia cells. Ting-Hsuan Wu, Lingfang Shi, Jessika Adrian, Minyi Shi, Ramesh V. Nair, Michael P. Snyder, Peter N. Kao

 

Insights into the molecular changes associated with postnatal human brain development: an integrated transcriptomics and proteomics study. Michael S. Breen, Sureyya Ozcan, Jordan M. Ramsey, Nitin Rustogi, Michael G. Gottshalk, Maree J. Webster, Cyndi Shannon Weickert, Joseph D. Buxbaum, Sabine Bahn

 

Mating can cause transgenerational gene silencing in Caenorhabditis elegans. Sindhuja Devanapally, Samual Allgood, Antony M. Jose

 

 

| Stem cells, regeneration & disease modelling

CATaDa reveals global remodelling of chromatin accessibility during stem cell differentiation in vivo. Gabriel N Aughey, Alicia Estacio Gomez, Jamie Thomson, Hang Yin, Tony D Southall

 

High-Resolution Dissection of Conducive Reprogramming Trajectory to Ground State Pluripotency. Asaf Zviran, Nofar Mor, Yoach Rais, Hila Gingold, Shani Peles, Elad Chomsky, Sergey Viukov, Jason D. Buenrostro, Leehee Weinberger, Yair S. Manor, Vladislav Krupalnik, Mirie Zerbib, Hadas Hezroni, Diego Adhemar Jaitin, David Larastiaso, Shlomit Gilad, Sima Benjamin, Awni Mousa, Muneef Ayyash, Daoud Sheban, Jonathan Bayerl, Alejandro Aguilera Castrejon, Rada Massarwa, Itay Maza, Suhair Hanna, Ido Amit, Yonatan Stelzer, Igor Ulitsky, William J. Greenleaf, Yitzhak Pilpel, Noa Novershtern, Jacob H. Hanna

 

SETDB1 prevents TET2-dependent activation of IAP retroelements in naïve embryonic stem cells. Özgen Deniz, Lorenzo de la Rica, Kevin C. L. Cheng, Dominik Spensberger, Miguel R. Branco

 

Sox4 drives intestinal secretory differentiation toward tuft and enteroendocrine fates. Adam Gracz, Matthew J. Fordham, Danny C. Trotier, Bailey Zwarycz, Yuan-Hung Lo, Katherine Bao, Joshua Starmer, Noah F. Shroyer, Richard L. Reinhardt, Scott T. Magness

 

FACT sets a barrier for cell fate reprogramming in C. elegans and Human. Ena Kolundzic, Andreas Ofenbauer, Bora Uyar, Anne Sommermeier, Stefanie Seelk, Mei He, Guelkiz Baytek, Altuna Akalin, Sebastian Diecke, Scott Allen Lacadie, Baris Tursun

 

Polymorphic dynamics of ribosomal proteins gene expression during somatic cell reprogramming and their differentiation into specialized cells-types. Prashanth Kumar Guthikonda, Sumitha Prameela Bharathan, Janakiram Rayabaram, Trinadha Rao Sornapudi, Sailu R Yellaboina, Shaji R Velayudhan, Sreenivasulu Kurukuti

 

Temporal epigenomic profiling identifies AHR as dynamic super-enhancer controlled regulator of mesenchymal multipotency. Deborah Gérard, Florian Schmidt, Aurélien Ginolhac, Martine Schmitz, Rashi Halder, Peter Ebert, Marcel H. Schulz, Thomas Sauter, Lasse Sinkkonen

 

Loss of MECP2 leads to induction of p53 and cell senescence. William E Lowry, Minori Ohashi, Peiyee Lee, Kai Fu, Benni Vargas, Denise E. Allen, Elena Korsakova, Jessica K Cinkornpumin, Carlos Salas, Jennifer C Park, Igal Germanguz, Konstantinos Chronis, Edward Kuoy, Stephen Tran, Xinshu Xiao, Matteo Pellegrini, Kathrin Plath

 

The U2AF homology motif kinase 1 (UHMK1) is upregulated upon hematopoietic cell differentiation. Isabella Barbutti, Joao Agostinho Machado-Neto, Vanessa Cristina Arfelli, Paula de Melo Campos, Fabiola Traina, Sara Teresinha Olalla Saad, Leticia Froehlich Archangelo

 

Integrated transcriptome and epigenome analyses identify alternative splicing as a novel candidate linking histone modifications to embryonic stem cell fate decision. Yungang Xu, Guangxu Jin, Liang Liu, Dongmin Guo, Xiaobo Zhou

 

Coronal sections of mice brains from Sullivan & Armstrong’s preprint

 

Transplanted Adult Neural Stem Cells Express Sonic Hedgehog In Vivo and Suppress White Matter Neuroinflammation After Experimental Traumatic Brain Injury. Genevieve M. Sullivan, eRegina C. Armstrong

 

Intraocular injection of ES cell-derived neural progenitors improve visual function in retinal ganglion cell-depleted mouse models. Divya Mundackal Sivaraman, Rasheed Vazhanthodi Abdul, Tiffany Schmidt, Lalitha Soundararajan, Samer Hattar, Jackson James

 

Transcriptional signatures of schizophrenia in hiPSC-derived NPCs and neurons are concordant with signatures from post mortem adult brains. Gabriel E. Hoffman, Brigham J. Hartley, Erin Flaherty, Ian Ladran, Peter Gochman, Douglas Ruderfer,Eli A. Stahl, Judith Rapoport, Pamela Sklar, Kristen J. Brennand

 

Part of Daniszewski, et al.’s experimental workflow

 

Single Cell RNA Sequencing of stem cell-derived retinal ganglion cells. Maciej Daniszewski, Anne Senabouth, Quan Nguyen, Duncan E Crombie, Samuel W Lukowski, Tejal Kulkarni, Donald J Zack, Alice Pebay, Joseph E Powell, Alex Hewitt

 

JIP2 haploinsufficiency contributes to neurodevelopmental abnormalities in human pluripotent stem cell-derived neural progenitors and cortical neurons. Reinhard Roessler, Johanna Goldmann, Chikdu Shivalila, Rudolf Jaenisch

 

LRP1 Regulates Peroxisome Biogenesis and Cholesterol Homeostasis in Oligodendrocytes and is Required in CNS Myelin Development and Repair. Jing-Ping Lin, Yevgeniya A Mironova, Peter Shrager, Roman J Giger

 

Effects of mechanical loading on cortical defect repair using a novel mechanobiological model of bone healing. Chao Liu, Robert Carrera, Vittoria Flamini, Lena Kenny, Pamela Cabahug-Zuckerman, Benson George, Daniel Hunter, Bo Liu, Gurpreet Singh, Philipp Leucht, Kenneth A Mann, Jill A Helms, Alesha B Castillo

 

Tracking responses to spinal cord injury in rats, from Didangelos, et al.’s preprint

 

Rats and axolotls share a common molecular signature after spinal cord injury enriched in collagen-1. Athanasios Didangelos, Katalin Bartus, Jure Tica, Michele Puglia, Bernd Roschitzki, Elizabeth Bradbury

 

DNAJB1-PRKACA fusion kinase drives tumorigenesis and interacts with β-catenin and the liver regenerative response. Edward R Kastenhuber, Gadi Lalazar, Darjus F Tschaharganeh, Shauna L Houlihan, Timour Baslan, Chi-Chao Chen, David Requena, Sha Tian, Benedikt Bosbach, John E Wilkinson, Sanford M Simon, Scott W Lowe

 

Bcl11b is a Newly Identified Regulator of Vascular Smooth Muscle Phenotype and Arterial Stiffness. Jeff Arni Valisno, Pavania Elavalakanar, Christopher Nicholson, Kuldeep Singh, Dorina Avram, Richard A. Cohen, Gary F. Mitchell, Kathleen G. Morgan, Francesca Seta

 

Chromatin accessibility profiling uncovers genetic- and T2D disease state-associated changes in cis-regulatory element use in human islets. Shubham Khetan, Romy Kursawe, Ahrim Youn, Nathan Lawlor, Eladio Marquez, Duygu Ucar, Michael L Stitzel

 

Drosophila larval brain neoplasms present tumour-type dependent genome instability. Fabrizio Rossi, Camille Stephan-Otto Attolini, Jose Luis Mosquera, Cayetano Gonzalez

 

Pervasive epistasis in cell proliferation pathways modulates neurodevelopmental defects of autism-associated 16p11.2 deletion. Janani Iyer, Mayanglambam Dhruba Singh, Matthew Jensen, Payal Patel, Lucilla Pizzo, Emily Huber, Haley Koerselman, Alexis T. Weiner, Paola Lepanto, Komal Vadodaria, Alexis Kubina, Qingyu Wang, Abigail Talbert, Sneha Yennawar, Jose Badano, J. Robert Manak, Melissa M. Rolls, Arjun Krishnan, Santhosh Girirajan

 

Targeting histone deacetylase activity to arrest cell growth and promote neural differentiation in Ewing sarcoma. Barbara Kunzler Souza, Patricia Luciana da Costa Lopez, Pamela Rossi Menegotto, Igor Araujo Vieira, Nathalia Kersting, Ana Lucia Abujamra, Andre T. Brunetto, Algemir L. Brunetto, Lauro Gregianin, Caroline Brunetto de Farias, Carol J. Thiele, Rafael Roesler

 

Fibroblast-derived HGF drives acinar lung cancer cell polarization through integrin-dependent RhoA-ROCK1 inhibition. Anirban Datta, Emma Sandilands, Keith E. Mostov, David M. Bryant

 

A Rational Drug Combination Design to Inhibit Epithelial-Mesenchymal Transition in a Three-Dimensional Microenvironment. Farnaz Barneh, Mehdi Mirzaie, Payman Nickchi, Tuan Zea Tan, Jean Paul Thiery, Mehran Piran, Mona Salimi, Fatemeh Goshadrou, Amir Reza Aref, Mohieddin Jafari

 

Telomerase mutant zebrafish from from Scahill, et al.’s preprint

 

The age of heterozygous telomerase mutant parents influences the adult phenotype of their offspring irrespective of genotype in zebrafish. Catherine M. Scahill1, Zsofia Digby, Ian M. Sealy, Richard J. White, John E. Collins, Elisabeth M. Busch-Nentwich

 

Evo-devo & evo

 

Distalless and engrailed expression in butterflies, from Connahs, et al.’s preprint

 

Disrupting different Distal-less exons leads to ectopic and missing eyespots accurately modeled by reaction-diffusion mechanisms. Heidi Connahs, Sham Tlili, Jelle van Creij, Tricia Y. J. Loo, Tirtha Banerjee, Timothy E. Saunders, Antonia Monteiro

 

The Complex Simplicity of the Brittle Star Nervous System. Olga Zueva, Maleana Khoury, Thomas Heinzeller, Daria Mashanova, Vladimir Mashanov

 

Early developmental morphology reflects independence from parents in social beetles. Kyle M. Benowitz, Madeline E. Sparks, Elizabeth C. McKinney, Patricia J. Moore, Allen J. Moore

 

A zombie LIF gene in elephants is up-regulated by TP53 to induce apoptosis in response to DNA damage. Juan Manuel Vazquez, Michael Sulak, Sravanthi Chigurupati, Vincent J. Lynch

 

Microinjection to deliver protein and mRNA into zygotes of the cnidarian endosymbiosis model Aiptasia sp. Madeline Bucher, Victor Arnold Shivas Jones, Elizabeth Ann Hambleton, Annika Guse

 

A core signaling mechanism at the origin of animal nociception. Oscar M. Arenas, Emanuela E. Zaharieva, Alessia Para, Constanza Vasquez-Doorman, Christian P. Petersen, Marco Gallio

 

Sphaeroforma arctica from Ondracka & Ruiz-Trillo’s preprint

 

Decoupling of the nuclear division cycle and cell size control in the coenocytic cycle of the ichthyosporean Sphaeroforma arctica. Andrej Ondracka, Iñaki Ruiz-Trillo

 

Pan-arthropod analysis reveals somatic piRNAs as an ancestral TE defence. Samuel H. Lewis, Kaycee A. Quarles, Yujing Yang, Melanie Tanguy, Lise Frezal, Stephen A. Smith, Prashant P. Sharma, Richard Cordaux, Clement Gilbert, Isabelle Giraud, David H. Collins, Phillip D. Zamore, Eric A. Miska, Peter Sarkies, Francis M. Jiggins

 

Multispecies coalescent analysis unravels the non-monophyly and controversial relationships of Hexapoda. Lucas A. Freitas, Beatriz Mello, Carlos G. Schrago

 

Repeat associated mechanisms of genome evolution and function revealed by the Mus caroli and Mus pahari genomes. David Thybert, Maša Roller, Fábio C. P. Navarro, Ian Fiddes, Ian Streeter, Christine Feig, David Martin-Galvez, Mikhail Kolmogorov, Václav Janoušek, Wasiu Akanni, Bronwen Aken, Sarah Aldridge, Varshith Chakrapani, William Chow, Laura Clarke, Carla Cummins, Anthony Doran, Matthew Dunn, Leo Goodstadt, Kerstin Howe, Matthew Howell, Ambre-Aurore Josselin, Robert C. Karn, Christina M. Laukaitis, Lilue Jingtao, Fergal Martin, Matthieu Muffato, Michael A. Quail, Cristina Sisu, Mario Stanke, Klara Stefflova, Cock Van Oosterhout, Frederic Veyrunes, Ben Ward, Fengtang Yang, Golbahar Yazdanifar, Amonida Zadissa, David Adams, Alvis Brazma, Mark Gerstein, Benedict Paten, Son Pham, Thomas Keane, Duncan T. Odom, Paul Flicek

 

Draft genome of the Eutardigrade Milnesium tardigradum sheds light on ecdysozoan evolution. Felix Mathias Bemm, Laura Burleigh, Frank Foerster, Roland Schmucki, Martin Ebeling, Christian Janzen, Thomas Dandekar, Ralph Schill, Ulrich Certa, Joerg Schultz

 

Bombyx mori from Qiao, et al.’s preprint

 

Melanism patches up the defective cuticular morphological traits through promoting the up-regulation of cuticular protein-coding genes in Bombyx mori. Liang Qiao, Ri-xin Wang, You-jin Hao, Hai Hu, Gao Xiong, Song-zhen He, Jiang-bo Song, Kun-peng Lu, James Mallet, Ya-qun Xin, Bin Chen, Fang-yin Dai

 

Genetic architectures of larval pigmentation and color pattern in the redheaded pine sawfly (Neodiprion lecontei). Catherine Linnen, Claire T. O’Quin, Taylor Shackleford, Connor R. Sears, Carita Lindstedt

 

Conserved microRNA targeting reveals preexisting gene dosage sensitivities that shaped amniote sex chromosome evolution. Sahin Naqvi, Daniel W Bellott, Kathy S Lin, David C Page

 

Radical changes persist longer in the absence of sex. Joel Sharbrough, Meagan Luse, Jeffrey L Boore, John M Logsdon Jr., Maurine Neiman

 

Gene transfers, like fossils, can date the Tree of Life. Adrian A. Davin, Eric Tannier, Tom A. Williams, Bastien Boussau, Vincent Daubin, Gergely J. Szollosi

 

Virtual Genome Walking: Generating gene models for the salamander Ambystoma mexicanum. Teri Evans, Andrew D. Johnson, Matthew D. Loose

 

Conflict between heterozygote advantage and hybrid incompatibility in haplodiploids (and sex chromosomes). Ana-Hermina Ghenu, Alexandre Blanckaert, Roger K. Butlin, Jonna Kulmuni, Claudia Bank

 

EVOLUTIONARY ANALYSIS OF CANDIDATE NON-CODING ELEMENTS REGULATING NEURODEVELOPMENTAL GENES IN VERTEBRATES. Francisco J. Novo

 

Dramatic evolution of body length due to post-embryonic changes in cell size in a newly discovered close relative of C. elegans. Gavin C. Woodruff, Patrick C. Phillips

 

The crowns have eyes: Multiple opsins found in the eyes of the Crown-of-Thorns Starfish Acanthaster planci including the first r-opsin utilized by a deuterostome eye. Elijah K. Lowe, Anders Garm, Esther Ullrich-Luter, Maria Ina Arnone

 

Evidence for “inter- and intraspecific horizontal genetic transfers” between anciently asexual bdelloid rotifers is explained by cross-contamination. Christopher G Wilson, Reuben W Nowell, Timothy G Barraclough

 

Cyanobacteria cell cize dynamics from Martins, et al.’s preprint

 

Cell size control driven by the circadian clock and environment in cyanobacteria. Bruno M. C. Martins, Amy K. Tooke, Philipp Thomas, James C. W. Locke

 

Cell biology

 

Wild type cilia from apical to basal, from Stevenson, et al.’s preprint

 

Regulator of calcineurin-2 is a ciliary protein with a role in cilia length control. Nicola Stevenson, Dylan Bergen, Amadeus Xu, Emily Wyatt, Freya Henry, Janine McCaughey, Laura Vuolo, Chrissy Hammond, David Stephens

 

Dynamics of the IFT Machinery at the Ciliary Tip. Alexander Chien, Sheng Min Shih, Raqual Bower, Douglas Tritschler, Mary E. Porter, Ahmet Yildiz

 

Dynamic Spatiotemporal Organization of Exocytosis During Cellular Shape Change. Fabio Urbina, Shawn Gomez, Stephanie L. Gupton

 

Microtubule regulation of integrin-based adhesions is mediated by myosin-IIA. Yukako Nishimura, Nisha Mohd Rafiq, Sergey V. Plotnikov, Zhen Zhang, Visalatchi Thiagarajan, Meenubharathi Natarajan, Gareth E. Jones, Pakorn Kanchanawong, Alexander D. Bershadsky

 

Force dependence of filopodia adhesion: involvement of myosin II and formins. Naila O. Alieva, Artem K. Efremov, Shiqiong Hu, Dongmyung Oh, Zhongwen Chen, Meenubharathi Natarajan, Hui Ting Ong, Antoine Jegou, Guillaume Romet-Lemonne, Jay T. Groves, Michael P. Sheetz, Jie Yan, Alexander D. Bershadsky

 

The lamellipodium is a myosin independent mechanosensor. Patrick W. Oakes, Tamara C. Bidone, Yvonne Beckham, Austin V. Skeeters, Guillermina R. Ramirez-San Juan, Stephen P. Winter, Gregory A. Voth, Margaret L. Gardel

 

Architecture of mammalian centriole distal appendages accommodates distinct blade and matrix functional elements. T. Tony Yang, Weng Man Chong, Won-Jing Wang, Gregory Mazo, Barbara Tanos, Zhengmin Chen, Minh Nguyet Thi Tran, Yi-De Chen, Rueyhung Roc Weng, Chia-En Huang, Wann-Neng Jane, Meng-Fu Bryan Tsou, Jung-Chi Liao

 

Spatial and temporal translocation of PKCα in single endothelial cell in response to focal mechanical stimulus. Masataka Arai, Toshihiro Sera, Takumi Hasegawa, Susumu Kudo

 

A Plk1 FRET reporter in action from Cascales, et al.’s preprint

 

Cyclin A2 localises in the cytoplasm at the S/G2 transition to activate Plk1. Helena Silva Cascales, Kamila Burdova, Erik Mullers, Henriette Stoy, Patrick von Morgen, Libor Macurek, Arne Lindqvist

 

CDK1 and PLK1 co-ordinate the disassembly and re-assembly of the Nuclear Envelope in vertebrate mitosis. Ines J de Castro, Raquel Sales Gil, Lorena Ligammari, Maria Laura Di Giacinto, Paola Vagnarelli

 

Phosphatase PP2A and microtubule pulling forces disassemble centrosomes during mitotic exit. Stephen J. Enos, Martin Dressler, Beatriz Ferreira Gomes, Anthony A. Hyman, Jeffrey B. Woodruff

 

Resolving ESCRT-III spirals at the intercellular bridge of dividing cells using 3D STORM imaging. Inna Goliand, Tali Dadosh, Natalie Elia

 

Reconstructing nuclear pores in Otsuka, et al.’s preprint

 

Postmitotic Nuclear Pore Assembly Proceeds By Radial Dilation Of Small ER Membrane Openings. Shotaro Otsuka, Anna M. Steyer, Martin Schorb, Jean-Karim Heriche, M. Julius Hossain, Suruchi Sethi, Moritz Kueblbeck, Yannick Schwab, Martin Beck, Jan Ellenberg

 

Nano-scale size holes in ER sheets provide an alternative to tubules for highly-curved membranes. Lena K. Schroeder, Andrew E.S. Barentine, Sarah Schweighofer, David Baddeley, Joerg Bewersdorf, Shirin Bahmanyar

 

Human replication licensing factor Cdt1 directly links mitotic kinetochores to spindle microtubules. Shivangi Agarwal, Kyle Smith, Yizhuo Zhou, Aussie Suzuki, Richard McKenney, Dileep Varma

 

Mutant worms from Beacham, et al.’s preprint

 

NECAPs are negative regulators of the AP2 clathrin adaptor complex. Gwendolyn M Beacham, Edward A Partlow, Jeffrey J Lange, Gunther Hollopeter

 

MDCK cells from Vivian Wang’s preprint

 

Propagating actomyosin-generated force to intercellular junction. Vivian W. Tang

 

Distinct prophase arrest mechanisms in human male meiosis. Sabrina Z. Jan, Aldo Jongejan, Cindy M. Korver, Saskia K. M. van Daalen, Ans M. M. van Pelt, Sjoerd Repping, Geert Hamer

 

ATR is a multifunctional regulator of male mouse meiosis. Alexander Widger, Shantha K Mahadevaiah, Julian Lange, Elias ElInati, Jasmin Zohren, Takayuki Hirota, Marcello Stanzione, Obah Ojarikre, Valdone Maciulyte, Dirk de Rooij, Attila Toth, Scott Keeney, James MA Turner

 

Non-canonical circadian oscillations in Drosophila S2 cells drive gene-expression cycles coupled to metabolic oscillations. Guillaume Rey, Nikolay B. Milev, Utham K. Valekunja, Ratnasekhar Ch, Sandipan Ray, Mariana Silva Dos Santos, Andras D. Nagy, Robin Antrobus, James I. MacRae, Akhilesh B. Reddy

 

The Cell-Cycle Transcriptional Network Generates and Transmits a Pulse of Transcription Once Each Cell Cycle. Chun-Yi Cho, Christina M. Kelliher, Steven B. Haase

 

Activation of Rho-kinase and focal adhesion kinase regulates the organization of stress fibers and focal adhesions in the central part of fibroblasts. Kazuo Katoh

 

Cell contraction induces long-ranged stress stiffening in the extracellular matrix. Yu Long Han, Pierre Ronceray, Guoqiang Xu, Andrea Malandrino, Roger Kamm, Martin Lenz, Chase P. Broedersz, Ming Guo

 

 

Modelling

Approximate Bayesian computation reveals the importance of repeated measurements for parameterising cell-based models of growing tissues. Jochen Kursawe, Ruth E. Baker, Alexander George Fletcher

 

Inferring parameters for a lattice-free model of cell migration and proliferation using experimental data. Alexander Browning, Scott W. McCue, Rachelle N. Binny, Michael J. Plank, Esha T. Shah, Matthew J. Simpson

 

Reprogramming, oscillations and transdifferentiation in epigenetic landscapes. Bivash Kaity, Ratan Sarkar, Buddhapriya Chakrabarti, Mithun K. Mitra

 

Modelling epigenetic dynamics, from Michieletto, et al.’s preprint

 

Shaping Epigenetic Memory via Genomic Bookmarking. Davide Michieletto, Michael Chiang, Davide Coli, Argyris Papantonis, Enzo Orlandini, Peter R. Cook, Davide Marenduzzo

 

Optimal quantification of contact inhibition in cell populations. David J. Warne, Ruth E. Baker, Matthew J. Simpson

 

In silico mechanobiochemical modeling of morphogenesis in cell monolayers. Hongyan Yuan, Bahador Marzban

 

Bifurcations in valveless pumping techniques from a coupled fluid-structure-electrophysiology model in heart development. Nicholas A. Battista, Laura A. Miller

 

Theory of epithelial cell shape transitions induced by mechanoactive chemical gradients. Kinjal Dasbiswas, Edouard Hannezo, Nir. S. Gov

 

Growing brains in silico, fromVerner & Garikipati’s preprint

 

A computational study of growth-driven folding patterns on shells, with application to the developing brain. S. N. Verner, K. Garikipati

 

Simulating insect wing shapes, from Ishimoto & Sugimura’s preprint

 

A mechanical model for diversified insect wing margin shapes. Yukitaka Ishimoto, Kaoru Sugimura

 

Analysis of biochemical mechanisms provoking differential spatial expression in Hh target genes. Manuel Cambón

 

The importance of geometry in the corneal micropocket assay. James A Grogan, Anthony J Connor, Joe M Pitt-Francis, Philip K Maini, Helen M Byrne

 

Functional Modeling of Plant Growth Dynamics. Yuhang Xu, Yumou Qiu, James Schnable

 

Integration of anatomy ontologies and Evo-Devo using structured Markov chains suggests a new framework for modeling discrete phenotypic traits. Sergei Tarasov

 

Spatial cytoskeleton organization supports targeted intracellular transport. Anne E. Hafner, Heiko Rieger

 

Consistent Reanalysis of Genome-wide Imprinting Studies in Plants Using Generalized Linear Models Increases Concordance across Datasets. Stefan Wyder, Michael T Raissig, Ueli Grossniklaus

 

Replication Timing Networks: a novel class of gene regulatory networks. Juan Carlos Rivera-Mulia, Sebo Kim, Haitham Gabr, Tamer Kahveci, David M Gilbert

 

 

Tools & resources

| Imaging etc.

Low cost and open source multi-fluorescence imaging system for teaching and research in biology and bioengineering. Isaac Nuñez, Tamara Matute, Roberto Herrera, Juan Keymer, Tim Marzullo, Tim Rudge, Fernan Federici

 

PhysiCell: an Open Source Physics-Based Cell Simulator for 3-D Multicellular Systems. Ahmadreza Ghaffarizadeh, Samuel H. Friedman, Shannon M. Mumenthaler, Paul Macklin

 

Hemodynamic forces can be accurately measured in vivo with optical tweezers. Sebastien Harlepp, Fabrice Thalmann, Gautier Follain, Jacky G. Goetz

 

Tracking chromosome dynamics from Ma, et al.’s preprint

 

CRISPR-Based DNA Imaging in Living Cells Reveals Cell Cycle-Dependent Chromosome Dynamics. Hanhui Ma, Li-Chun Tu, Ardalan Naseri, Yu-Chieh Chung, David Grunwald, Shaojie Zhang, Thoru Pederson

 

Simultaneously measuring image features and resolution in live-cell STED images. Andrew E. S. Barentine, Lena K. Schroeder, Michael Graff, David Baddeley, Joerg Bewersdorf

 

Obtaining 3D Super-resolution Information from 2D Super-resolution Images through a 2D-to-3D Transformation Algorithm. Andrew Ruba, Joseph Kelich, Wangxi Luo, Weidong Yang

 

Hydrogel encapsulation of living organisms for long-term microscopy. Kyra Burnett, Eric Edsinger, Dirk R. Albrecht

 

Quantification of cellular distribution as Poisson process in 3D matrix using a multiview light-sheet microscope. Warren Colomb, Matthew Osmond, Charles Durfee, Melissa D. Krebs, Susanta K. Sarkar

 

Replication domains from Xiang, et al.’s preprint

 

Correlative live and super-resolution imaging reveals the dynamic structure of replication domains. Wanqing Xiang, M. Julia Roberti, Jean-Karim Heriche, Sebastian Huet, Stephanie Alexander, Jan Ellenberg

 

Coupling optogenetics and light-sheet microscopy to study signal transduction in vivo. Prameet Kaur, Timothy E. Saunders, Nicholas Stanislaw Tolwinski

 

Arabidopsis phenotyping through Geometric Morphometrics. Carlos A. Manacorda, Sebastian Asurmendi

 

MICCS: A Fully Programmable Multipurpose Integrated Cell Culture System. Timothy Kassis, Paola M. Perez, Chloe J. W. Yang, Luis R. Soenksen, David L. Trumper, Linda G. Griffith

 

vU-net: accurate cell edge segmentation in time-lapse fluorescence live cell images based on convolutional neural network. Chuangqi Wang, Xitong Zhang, Yenyu Chen, Kwonmoo Lee

 

ChromoTrace: Reconstruction of 3D Chromosome Configurations by Super-Resolution Microscopy. Carl Barton, Sandro Morganella, Oeyvind Oedegaard, Stephanie Alexander, Jonas Ries, Tomas Fitzgerald, Jan Ellenberg, Ewan Birney

 

PlantCV v2.0: Image analysis software for high-throughput plant phenotyping. Malia A Gehan, Noah Fahlgren​​, Arash Abbasi, Jeffrey C Berry, Steven T Callen, Leonardo Chavez, Andrew N Doust, Max J Feldman, Kerrigan B Gilbert, John G Hodge, J Steen Hoyer, Andy Lin, Suxing Liu, César Lizárraga, Argelia Lorence, Michael Miller, Eric Platon, Monica Tessman, Tony Sax

 

Segmented plants with help from Rasberry Pi, from Tovar, et al.’s prperint

 

Raspberry Pi Powered Imaging for Plant Phenotyping. Jose Tovar, John Steen Hoyer, Andy Lin, Allison Tielking, Steven Callen, Elizabeth Castillo, Michael Miller, Monica Tessman, Noah Fahlgren, James Carrington, Dmitri Nusinow, Malia A. Gehan

 

Segmenting Calcium flashes in Reynolds, et al.’s preprint

 

ABLE: an Activity-Based Level Set Segmentation Algorithm for Two-Photon Calcium Imaging Data. Stephanie Reynolds, Therese Abrahamsson, Renaud Schuck, P. Jesper Sjöström, Simon R Schultz, Pier Luigi Dragotti

 

Edge Detection of Cryptic Lamellipodia Assisted by Deep Learning. Chuangqi Wang, Shawn Kang, Eunice Kim, Xitong Zhang, Hee June Choi, Aaron Choi, Kwonmoo Lee

 

Mapping nonapoptotic caspase activity with a transgenic reporter in mice. Peter Nicholls, Thomas Pack, Nikhil Urs, Sunil Kumar, Gabor Turu, Evan Calabrese, Wendy Roberts, Ping Fan, Valeriy Ostapchenko, Monica Guzman, Flavio Beraldo, Vania Prado, Marco Prado, Ivan Spasojevic, Joshua Snyder, Kafui Dzirasa, G. Allan Johnson, Marc Caron

 

Development of an Intrinsic Skin Sensor for Blood Glucose Level with CRISPR-mediated Genome Editing in Epidermal Stem Cells. Jiping Yue, Yuanyuan Li, Xuewen Gou, Xiaoyang Wu

 

Mini-ring approach for high-throughput drug screenings in 3D tumor models. Nhan Phan, Bobby Tofig, Deanna Janzen, Jin Huang, Sanaz Memarzadeh, Robert Damoiseaux, Alice Soragni

 

A Cautionary Tail: Changes in Integrin Behavior with Labeling. Catherine G. Galbraith, Michael W. Davidson, James A. Galbraith

 

| Genome tools

Employing single-stranded DNA donors for the high-throughput production of conditional knockout alleles in mice. Denise G. Lanza, Angelina Gaspero, Isabel Lorenzo, Lan Liao, Ping Zheng, Ying Wang, Yu Deng, Chonghui Cheng, Chuansheng Zhang, Matthew N. Rasband, John R. Seavitt, Francisco J. DeMayo, Jianming Xu, Mary E. Dickinson, Arthur L. Beaudet, Jason D. Heaney

 

Generation and validation of homozygous fluorescent knock-in cells using genome editing. Birgit Koch, Bianca Nijmeijer, Moritz Kueblbeck, Yin Cai, Nike Walther, Jan Ellenberg

 

Precision genome-editing with CRISPR/Cas9 in human induced pluripotent stem cells. John P. Budde, Rita Martinez, Simon Hsu, Natalie Wen, Jason A. Chen, Giovanni Coppola, Alison M. Goate, Carlos Cruchaga, Celeste Karch

 

Unexpected CRISPR off-target mutation pattern in vivo are not typically germline-like. Zhiting Wei, Funan He, Guohui Chuai, Hanhui Ma, Zhixi Su, Qi Liu

 

Crossing enhanced and high fidelity SpCas9 nucleases to optimize specificity and cleavage. Peter Istvan Kulcsar, Andras Talas, Krisztina Huszar, Zoltan Ligeti, Eszter Toth, Nora Weinhardt, Elfrieda Fodor, Ervin Welker

 

High-throughput creation and functional profiling of eukaryotic DNA sequence variant libraries using CRISPR/Cas9. Xiaoge Guo, Alejandro Chavez, Angela Tung, Yingleong Chan, Ryan Cecchi, Santiago Lopez Garnier, Christian Kaas, Eric Kelsic, Max Schubert, James DiCarlo, James Collins, George Church

 

FlashFry: a fast and flexible tool for large-scale CRISPR target design. Aaron McKenna, Jay Shendure

 

CRISPRd Arabidopsis from Hodgens, et al.’s preprint

 

indCAPS: A tool for designing screening primers for CRISPR/Cas9 mutagenesis events. Charles Hodgens, Zachary Nimchuk, Joseph Kieber

 

Integrated design, execution, and analysis of arrayed and pooled CRISPR genome editing experiments. Matthew C. Canver, Maximilian Haeussler, Daniel E. Bauer, Stuart H. Orkin, Neville E. Sanjana, Ophir Shalem, Guo-Cheng Yuan, Feng Zhang, Jean-Paul Concordet, Luca Pinello

 

Mechanisms of improved specificity of engineered Cas9s revealed by single molecule analysis. Digvijay Singh, Yanbo Wang, John Mallon, Olivia Yang, Jingyi Fei, Anustup Poddar, Damon Ceylan, Scott Bailey, Taekjip Ha

 

Characterization and Validation of a Novel Group of Type V, Class 2 Nucleases for in vivo Genome Editing. Matthew B Begemann, Benjamin N Gray, Emma January, Anna Singer, Dylan C Kesler, Yonghua He, Haijun Liu, Hongjie Guo, Alex Jordan, Thomas P Brutnell, Todd C Mockler, Mohammed Oufattole

 

High-resolution genome-wide functional dissection of transcriptional regulatory regions in human. Xinchen Wang, Liang He, Sarah Goggin, Alham Saadat, Li Wang, Melina Claussnitzer, Manolis Kellis

 

Multi-platform​ ​ discovery​ ​ of​ ​ haplotype-resolved structural​ ​ variation​ ​ in​ ​ human​ ​ genomes. Mark J.P. Chaisson, Ashley D. Sanders, Xuefang Zhao, Ankit Malhotra, David Porubsky, Tobias Rausch, Eugene J. Gardner, Oscar Rodriguez, Li Guo, Ryan L. Collins, Xian Fan, Jia Wen, Robert E. Handsaker, Susan Fairley, Zev N. Kronenberg, Xiangmeng Kong, Fereydoun Hormozdiari, Dillon Lee, Aaron M. Wenger, Alex Hastie, Danny Antaki, Peter Audano, Harrison Brand, Stuart Cantsilieris, Han Cao, Eliza Cerveira, Chong Chen, Xintong Chen, Chen-Shan Chin, Zechen Chong, Nelson T. Chuang, Deanna M. Church, Laura Clarke, Andrew Farrell, Joey Flores, Timur Galeev, Gorkin David, Madhusudan Gujral, Victor Guryev, William Haynes-Heaton, Jonas Korlach, Sushant Kumar, Jee Young Kwon, Jong Eun Lee, Joyce Lee, Wan-Ping Lee, Sau Peng Lee, Patrick Marks, Karine Valud-Martinez, Sascha Meiers, Katherine M. Munson, Fabio Navarro, Bradley J. Nelson, Conor Nodzak, Amina Noor, Sofia Kyriazopoulou-Panagiotopoulou, Andy Pang, Yunjiang Qiu, Gabriel Rosanio, Mallory Ryan, Adrian Stutz, Diana C.J. Spierings, Alistair Ward, AnneMarie E. Welsch, Ming Xiao, Wei Xu, Chengsheng Zhang, Qihui Zhu, Xiangqun Zheng-Bradley, Goo Jun, Li Ding, Chong​ ​ Lek Koh, Bing Ren, Paul Flicek, Ken Chen, Mark B. Gerstein, Pui-Yan Kwok, Peter M. Lansdorp, Gabor Marth, Jonathan Sebat, Xinghua Shi, Ali Bashir, Kai Ye, Scott E. Devine, Michael Talkowski, Ryan E. Mills, Tobias Marschall, Jan Korbel, Evan E. Eichler, Charles Lee

 

Successful optimization of CRISPR/Cas9-mediated defined point mutation knock-in using allele-specific PCR assays in zebrafish. Sergey V. Prykhozhij, Charlotte Fuller, Shelby L. Steele, Chansey J. Veinotte, Babak Razaghi, Christopher McMaster, Adam Shlien, David Malkin, Jason N. Berman

 

Profiling DNA Methylation Differences Between Inbred Mouse Strains on the Illumina Human Infinium MethylationEPIC Microarray. Hemant Gujar, Jane W Liang, Nicholas C Wong, Khyobeni Mozhui

 

From trash to treasure: detecting unexpected contamination in unmapped NGS data. llaria Granata​​, Mara Sangiovanni​​, Amarinder Singh Thind, Mario Rosario Guarracino.

 

Accurate estimation of molecular counts in droplet-based single-cell RNA-seq experiments. Viktor Petukhov, Jimin Guo, Ninib Baryawno, Nicolas Severe, David Scadden, Maria G. Samsonova, Peter V. Kharchenko

 

Gene synthesis allows biologists to source genes from farther away in the tree of life. Aditya Kunjapur, Philipp Pfingstag, Neil C Thompson

 

Curated compendium of human transcriptional biomarker data. Nathan P Golightly, Anna I Bischoff, Avery Bell, Parker D Hollingsworth, Stephen R Piccolo

 

One of Hansen,  et al.’s subcellular process networks

 

A flexible ontology for inference of emergent whole cell function from relationships between subcellular processes. Jens Hansen, David Meretzky, Simeneh Woldesenbet, Gustavo Stolovitzky, Ravi Iyengar

 

Comparison of seven single cell Whole Genome Amplification commercial kits using targeted sequencing. Tamir Biezuner, Ofir Raz, Shiran Amir, Lilach Milo, Rivka Adar, Yael Fried, Elena Ainbinder, Ehud Shapiro

 

Biosensor libraries harness large classes of binding domains for allosteric transcription regulators. Javier F. Juarez, Begoña Lecube-Azpeitia, Stuart L. Brown, George M. Church

 

An automated model test system for systematic development and improvement of gene expression models. Alexander C Reis, Howard Salis

 

Using DNase Hi-C techniques to map global and local three-dimensional genome architecture at high resolution. Wenxiu Ma, Ferhat Ay, Choli Lee, Gunhan Gulsoy, Xinxian Deng, Savannah Cook, Jennifer Hesson, Christopher Cavanaugh, Carol B. Ware, Anton Krumm, Jay Shendure, C. Anthony Blau, Christine M. Disteche, William S. Noble, Zhijun Duan

 

Massive Mining of Publicly Available RNA-seq Data from Human and Mouse. Alexander Lachmann, Denis Torre, Alexandra B. Keenan, Kathleen M. Jagodnik, Hyojin J. Lee, Moshe C. Silverstein, Lily Wang, Avi Ma’ayan

 

LeafCutter: Annotation-free quantification of RNA splicing. Yang I. Li, David A. Knowles, Jack Humphrey, Alvaro N. Barbeira, Scott P. Dickinson, Hae Kyung Im, Jonathan K. Pritchard

 

A sequence-based, deep learning model accurately predicts RNA splicing branchpoints. Joseph M. Paggi, Gill Bejerano

 

Superior ab initio Identification, Annotation and Characterisation of TEs and Segmental Duplications from Genome Assemblies. LU ZENG, R Daniel Kortschak, Joy M Raison, Terry Bertozzi, David L Adelson

 

DeepBlueR: Large-scale epigenomic analysis in R. Markus List, Felipe Albrecht, Christoph Bock, Thomas Lengauer

 

mosdepth: quick coverage calculation for genomes and exomes. Brent S. Pedersen, Aaron Quinlan

 

CUT&RUN: Targeted in situ genome-wide profiling with high efficiency for low cell numbers. Peter J. Skene, Steven Henikoff

 

Real-time fluorescence and deformability cytometry – flow cytometry goes mechanics. Philipp Rosendahl, Katarzyna Plak, Angela Jacobi, Martin Kraeter, Nicole Toepfner, Oliver Otto, Christoph Herold, Maria Winzi, Maik Herbig, Yan Ge, Salvatore Girardo, Katrin Wagner, Buzz Baum, Jochen Guck

 

DAFi: A Directed Recursive Filtering and Clustering Approach to Data-Driven Identification of Cell Populations from Polychromatic Flow Cytometry Data. Alexandra J Lee, Ivan Chang, Julie G Burel, Cecilia S Lindestam Arlehamn, Daniela Weiskopf, Bjoern Peters, Alessandro Sette, Richard H Scheuermann, Yu Qian

 

Interactive Visual Analysis of Mass Cytometry Data by Hierarchical Stochastic Neighbor Embedding Reveals Rare Cell Types. Vincent van Unen, Thomas Hollt, Nicola Pezzotti, Na Li, Marcel J. T. Reinders, Elmar Eisemann, Anna Vilanova, Frits Koning, Boudewijn P. F. Lelieveldt

 

HyperTRIBE: Upgrading TRIBE with enhanced editing. Weijin Xu, Reazur Rahman, Michael Rosbash

 

plot2DO: a tool to assess the quality and distribution of genomic data. Răzvan V Chereji

 

Gene regulatory network inference from single-cell data using multivariate information measures. Thalia E Chan, Michael Stumpf, Ann C Babtie

 

A duplex MIPs-based biological-computational cell lineage discovery platform. Liming Tao, Ofir Raz, Zipora Marx, Tamir Biezuner, Shiran Amir, Lilach Milo, Rivka Adar, Amos Onn, Noa Chapal-Ilani, Veronika Berman, Ron Levy, Barak Oron, Ehud Shapiro

 

Deep learning of the splicing (epi)genetic code reveals a novel candidate mechanism linking histone modifications to ESC fate decision. Yungang Xu, Yongcui Wang, Jiesi Luo, Weiling Zhao, Xiaobo Zhou

 

miRNAgFree: prediction and profiling of novel microRNAs without genome assembly. Ernesto L. Aparicio, Antonio Rueda, Bastian Fromm, Cristina Gómez-Martin, Ricardo Lebrón, Jose L Oliver, Juan A Marchal, Michail Kotsyfakis, Michael Hackenberg

 

Trendy: Segmented regression analysis of expression dynamics for high-throughput ordered profiling experiments. Rhonda Bacher, Ning Leng, Li-Fang Chu, James Thomson, Christina Kendziorski, Ron Stewart

 

MTopGO: a tool for module identification in PPI Networks. Danila Vella​, Simone Marini, Francesca Vitali, Riccardo Bellazzi

 

Research practice

Award or Reward? Which comes first, NIH funding or research impact? Lucas C Parra, Lukas Hirsch

 

Assessment of the impact of shared data on the scientific literature. Michael  Milham, Cameron Craddock, Michael Fleischmann, Jake Son, Jon Clucas, Helen Xu, Bonhwang Koo, Anirudh Krishnakumar, Bharat Biswal, Francisco Castellanos, Stan Colcombe, Adriana Di Martino, Xi-Nian Zuo, Arno Klein

 

IntelliEppi: Intelligent reaction monitoring and holistic data management system for the molecular biology lab. Arthur Neuberger, Zeeshan Ahmed, Thomas Dandekar

 

Findings of a retrospective, controlled cohort study of the impact of a change in Nature journals’ editorial policy for life sciences research on the completeness of reporting study design and execution. Malcolm Robert Macleod, The NPQIP Collaborative group

 

A persistent lack of International representation on editorial boards in environmental biology. Johanna Espin, Sebastian Palmas-Perez,Farah Carrasco-Rueda, Kristina Riemer, Pablo Allen, Nathan Berkebile, Kirsten Hecht, Renita Kay Kastner-Wilcox, Mauricio Nunez-Regueiro, Candice Prince, Maria Constanza Rios-Marin, Erica P. Ross, Bhagatveer Sangha, Tia Tyler, Judit Ungvari-Martin, Mariana Villegas, Tara Cataldo, Emilio Bruna

 

Idea farming: it is a good idea to have bad ideas in science. Christopher J Lortie

 

Imagining the ‘open’ university: Sharing scholarship to improve research and education. Erin C McKiernan

 

The Modern Research Data Portal: A design pattern for networked, data-intensive science. Kyle Chard, Eli Dart, Ian Foster​, David Shifflett, Steven Tuecke, Jason Williams

 

Can editors save peer review from peer reviewers? Rafael D’Andrea, James P O’Dwyer.

 

How to share data for collaboration. Shannon E Ellis, Jeffrey T Leek

 

An invitation to modeling: building a community with shared explicit practices. Kam D Dahlquist, Melissa L Aikens, Joseph T Dauer, Samuel S Donovan, Carrie Diaz Eaton, Hannah Callender Highlander, Kristin P Jenkins, John R Jungck, M Drew LaMar, Glenn Ledder, Robert L Mayes, Richard C Schugart

 

Down with ncRNA! Long live fRNA and jRNA! Dan Graur

 

What exactly is ‘N’ in cell culture and animal experiments? Stanley E Lazic, Charlie J Clarke-Williams, Marcus R Munafo

 

Estimating the scale of biomedical data generation using text mining. Gabriel Rosenfeld, Dawei Lin

 

Why not…

 

Sand-bubbler crab-inspired algorithm art from Hendrik Richter

 

Visual art inspired by the collective feeding behavior of sand-bubbler crabs. Hendrik Richter

 

The reality of “food porn”: Larger brain responses to food-related cues than to erotic images predict cue-induced eating. Francesco Versace, David W Frank, Elise M Stevens, Menton M Deweese, Michele Guindani, Susan M Schembre

Thumbs up (1 votes)
Loading...

Tags:
Categories: Highlights

In Development this week (Vol. 144, Issue 19)

Posted by , on 3 October 2017

Here are the highlights from the current issue of Development:

 

Making a move: EMT holds the key to planarian regeneration

Embedded Image

During development and wound healing, progenitor cells are required to migrate to different locations before they can differentiate into terminal tissue types. This cell migration often involves epithelial-to-mesenchymal transition (EMT), a process by which cells delaminate from an epithelium and become motile. On page 3440, Aziz Aboobaker and colleagues investigate how neoblasts, the adult stem cell population present in planarians, are able to migrate to sites of damage in order to regenerate tissue after irradiation. Using a shielded X-ray irradiation assay, they show that neoblasts require β-integrin and the activity of a matrix metalloproteinase to interact with the extracellular matrix and move through the tissue, just as in EMT. In addition, they show that migration requires EMT-associated transcription factor orthologs, such as snail-1snail-2 and zeb-1. Strikingly, the differentiation status of cells also affects their ability to migrate. Finally the authors report that, even in the absence of wounding, a notum-dependent signal from the brain, which normally lacks resident stem cells, draws in migrating neoblasts to maintain tissue homeostasis. Together, these results suggest that EMT-related mechanisms controlling cell migration are conserved among bilaterians and provide insights into how progenitor populations move to a site of wounding before regeneration begins.

 

How mouse oocytes give DNA damage the SAC

Embedded Image

Cells in embryos and adult tissues have mechanisms that allow them to identify and respond to DNA damage, thereby ensuring that deleterious mutations cannot arise and persist in individuals. On page 3475, Keith Jones and colleagues investigate the mechanism by which mouse oocytes arrest upon DNA damage. This response involves activation of the spindle assembly checkpoint (SAC), which normally prevents the onset of anaphase until all chromosomes are correctly attached to the spindle. In this study, the authors find that, within minutes of DNA damage, SAC-associated proteins are not recruited to the sites of damage along chromosome arms, but instead become concentrated at the chromosome kinetochores, which act as a platform to generate the SAC signal. SAC activation is dependent on the activity of aurora kinase and MPS1 kinase but, interestingly, does not rely on PI3K-related kinases important for the DNA damage response in other systems. Furthermore, the authors show that the arrest response is unique to oocytes in meiosis I and does not occur in oocytes undertaking meiosis II. These results uncover a new mechanism by which DNA damage is dealt with in oocytes and provide clues into how the formation of genetically abnormal embryos is prevented.

 

Imp and Syp call time on Drosophila neuroblasts

Embedded Image

Drosophila neurons are born from progenitors, known as neuroblasts, in a temporally controlled manner. Given that the timing of birth affects the type of neuron that is generated, this process must be tightly regulated over time so that a diverse array of neuronal progeny is produced. The RNA-binding proteins IGF-II mRNA-binding protein (Imp) and 15 Syncrip/hnRNPQ (Syp) are known to exhibit temporally graded expression patterns in neuroblasts, and have thus been shown to regulate the process of neuronal fate specification. Now, on page 3454, Tzumin Lee and colleagues uncover a role for Imp and Syp in neuroblast decommissioning, as well as in neuron differentiation. ‘Decommissioning’ is the process by which neuroblasts shrink and exit the self-renewing progenitor state before forming terminally differentiated neurons. The authors find that Imp and Syp are crucial for this two-stage ‘decommissioning’ process. Imp regulates shrinkage of the neuroblast so that this event does not occur prematurely, while Syp acts subsequently to promote the accumulation of Prospero in the nucleus, leading to cell-cycle exit. Together, these results provide a mechanism by which neuroblast decommissioning occurs in the Drosophila brain and enhance our understanding of how neural stem cells are controlled during development.

 

PLUS:

 

An interview with Jayaraj Rajagopal

Embedded ImageJayaraj (Jay) Rajagopal is a Principal Investigator at the Center for Regenerative Medicine at Massachusetts General Hospital and an Associate Professor of Medicine at Harvard Medical School. His lab works on the development and regeneration of the lung, using stem cell and animal models to develop novel insights that hopefully will provide inspiration for therapies to help treat human lung disease. In 2017, he was awarded the Dr Susan Lim Award for Outstanding Young Investigator at the International Society for Stem Cell Research (ISSCR) meeting in Boston (MA,USA), where we met him to talk about how a fish tank started a life-long fascination with the lung, the transition to running his own lab, and his optimism for the future of both basic stem cell research and its clinical translation. Read the Spotlight article on p. 3389.

 

On the evolution of bilaterality

Fig. 1.Bilaterality – the possession of two orthogonal body axes – is the name-giving trait of all bilaterian animals. These body axes are established during early embryogenesis and serve as a three-dimensional coordinate system that provides crucial spatial cues for developing cells, tissues, organs and appendages. How bilaterality evolved and whether it evolved once or several times independently is a fundamental issue in evolutionary developmental biology. Recent findings from non-bilaterian animals, in particular from Cnidaria, the sister group to Bilateria, have shed new light into the evolutionary origin of bilaterality. In their Hypothesis article, Grigory Genikhovich and Ulrich Technau compare the molecular control of body axes in radially and bilaterally symmetric cnidarians and bilaterians, identify the minimal set of traits common for Bilateria, and evaluate whether bilaterality arose once or more than once during evolution.

 

The PAR proteins: from molecular circuits to dynamic self-stabilizing cell polarity

Fig. 1.PAR proteins constitute a highly conserved network of scaffolding proteins, adaptors and enzymes that form and stabilize cortical asymmetries in response to diverse inputs. They function throughout development and across the metazoa to regulate cell polarity. In recent years, traditional approaches to identifying and characterizing molecular players and interactions in the PAR network have begun to merge with biophysical, theoretical and computational efforts to understand the network as a pattern-forming biochemical circuit. In their Review article, Charles Lang and Edwin Munro summarize recent progress in the field, focusing on recent studies that have characterized the core molecular circuitry, circuit design and spatiotemporal dynamics.

 

 

Can injured adult CNS axons regenerate by recapitulating development?

In the adult mammalian central nervous system (CNS), neurons typically fail to regenerate their axons after injury. During development, by contrast, neurons extend axons effectively. A variety of intracellular mechanisms mediate this difference, including changes in gene expression, the ability to form a growth cone, differences in mitochondrial function/axonal transport and the efficacy of synaptic transmission. In turn, these intracellular processes are linked to extracellular differences between the developing and adult CNS. During development, the extracellular environment directs axon growth and circuit formation. In adulthood, by contrast, extracellular factors, such as myelin and the extracellular matrix, restrict axon growth. In their Review article, Brett Hilton and Frank Bradke, we discuss whether the reactivation of developmental processes can elicit axon regeneration in the injured CNS.

 

 

 

 

Thumbs up (No Ratings Yet)
Loading...

Categories: Research

Center for Stem Cell and Organoid Medicine (CuSTOM) Faculty

Posted by , on 2 October 2017

Closing Date: 15 March 2021

The new Center for Stem Cell & Organoid Medicine (CuSTOM) at Cincinnati Children’s Hospital Medical Center (CCHMC) is launching a major new initiative to recruit outstanding tenure-track or tenured faculty at the Assistant to Associate Professor level.

 

CuSTOM  (https://www.cincinnatichildrens.org/research/divisions/c/custom) is a multi-disciplinary center of excellence integrating developmental and stem cell biologists, clinicians, bioengineers and entrepreneurs with the common goal of accelerating discovery and facilitating bench-to-bedside translation of organoid technology and regenerative medicine. Faculty in CuSTOM benefit from the unique environment and resources here to accelerate their studies of human development, disease and regenerative medicine using organoid platforms.

 

CCHMC is a leader in organoid biology and one of the top ranked pediatric research centers in the world, providing a unique environment for basic and translational research. Among pediatric institutions CCHMC is the third-highest ranking recipient of research grants from the National Institutes of Health. CCHMC continues to make major investments in research supporting discovery with 1.4 million square feet of research space and subsidized state-of-the-art core facilities including a human pluripotent stem cell facility, genome editing, high-throughput DNA analysis, biomedical informatics, a Nikon Center of Excellence imaging core and much more.

 

We invite applications from innovative and collaborative investigators focused on basic or translational research in human development and/or disease using stem cells or organoid models. Successful candidates must hold the PhD, MD, or MD/PhD degrees, and will have a vibrant research program with an outstanding publication record.

 

Applicants should submit their curriculum vitae, two to three page research statement focused on future plans, and contact information for three people who will provide letters of recommendation to CuSTOM@cchmc.org.  Applications must be submitted by January 5, 2018.

 

The Cincinnati Children’s Hospital Medical Center, and the University of Cincinnati are Affirmative Action/Equal Opportunity Employers. Qualified women and minority candidates are especially encouraged to apply.

Thumbs up (No Ratings Yet)
Loading...

Categories: Jobs