Salary: £37,382 – £47,314

Fixed-term: The funds for this post are available until 30 November 2017 in the first instance.

As part of the UK Regenerative Medicine Platform (UKRMP), three UK Research Councils; Biotechnology and Biological Sciences Research Council, Engineering and Physical Sciences Research Council and the Medical Research Council have invested £25m in research and equipment to support the development of regenerative medicine therapies for a range of applications.

The Pluripotent Stem Cell Hub has been awarded £4.5m to establish a collaboration which brings together researchers from industry and academia to develop the processes needed to take these cells from laboratory-based research to the commercial manufacture of safe, effective and reproducible products for use in regenerative medicine.  The Hub will work with the other strands of the UKRMP to tackle some of the critical challenges in developing new regenerative treatments from discoveries made in the lab (www.ukrmp.org.uk).

For exceptional candidates it may be possible to appoint up to the top of Grade 9 (£48,729-£53,233).  In addition, it may be possible to offer a supplement to the salary range stated for this role any such supplement would be awarded on the basis of a demonstrable history of exceptional achievement and is entirely at the discretion of the University

An exciting opportunity for a Project Manager who has held a senior management role in a complex environment and a proven track record in business/ bioindustry whilst empathising with academic ethos.

We are looking for a highly motivated individual to manage projects effectively according to industry best practice, determining and delivering to agreed scope, quality, budget and deadlines. The Project Manager will manage a number of projects concurrently and will maintain accurate project plans, work schedules, issue and risk logs to enable projects to be delivered successfully.

The successful applicant will be commercially astute, intellectually agile with excellent communication skills.

The successful applicant will be educated to at least degree level and have a further qualification (MSC, PhD or MBA).  You will be able to demonstrate your ability to build effective relationships with funders, Engage with experts worldwide, develop summary documents and reports, organisation meetings and associated administration, and work related communication.  Hands on experience of budgeting, grant applications and other administrative tasks in a research- led environment would be highly advantageous as would experience of working as part of a senior management team with budgetary responsibility and accountability for group and individual performance.

The role-holder will be a confident and articulate communicator and will possess a highly collaborative and inspirational leadership style with a track record of managing and developing multi-disciplinary teams as well as building relationships with external partners.

Based in central Cambridge, you must be willing to travel between the partner sites.

Once an offer of employment has been accepted, the successful candidate will be required to undergo a health assessment.

To apply, please visit our vacancies webpage: http://www.stemcells.cam.ac.uk/careers-study/vacancies/

Informal enquiries are also welcome via email to: cscrjobs@cscr.cam.ac.uk

Applications must be submitted by 17:00 on the closing date of Friday 6th December 2013.

Interviews will be held in the week commencing 16th December 2013. If you have not been invited for interview by 12th December 2013, you have not been successful on this occasion.

Please quote reference PS02099 on your application and in any correspondence about this vacancy.

The University values diversity and is committed to equality of opportunity.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.

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TWO-YEAR VISITING ASSISTANT PROFESSOR

CELL AND DEVELOPMENTAL BIOLOGY

Department of Biology, Swarthmore College

The Department of Biology at Swarthmore College invites applications for a two-year visiting assistant professor position for the 2014-15 and 2015-16 academic years. Teaching responsibilities include participation in a team-taught introductory biology course as well as teaching intermediate-level courses with weekly laboratories in cell biology (2014-15) and developmental biology (2015-16).  Additionally, there may be an opportunity to teach an advanced seminar-style course (with laboratory projects) in an area that is complementary to our existing curriculum.

Applicants should have a Ph.D., teaching experience, and a strong commitment to undergraduate education. The College provides laboratory space and funds to support student research and faculty travel.  The Biology Department is dedicated to educating and supporting a rich, diverse body of students and encourages candidates who will further advance the goals of fostering an inclusive community with diverse ideas and experiences.  All application materials (curriculum vitae, statements of teaching and research interests, and three letters of recommendation) should be submitted online at https://academicjobsonline.org/ajo/jobs/3578 by January 13^th, 2014. For more information, please visit our website at www.swarthmore.edu/biology. Questions regarding this position should be addressed to the Biology Department chair, Amy Cheng Vollmer, at avollme1@swarthmore.edu or by calling 610-328-8044.

Swarthmore College is a highly selective liberal arts college, located in the suburbs of Philadelphia,whose mission combines academic rigor with social responsibility.  Swarthmore has a strong institutional commitment to inclusive excellence through diversity in its educational program and employment practices.  The College actively seeks and welcomes applications from candidates with exceptional qualifications, particularly those with demonstrable commitments to a more inclusive society and world.

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This interview first appeared in Development.

Benoit Bruneau is a developmental biologist based at the Gladstone Institutes in San Francisco. His lab studies the transcription factors and chromatin remodelling complexes that regulate cardiac organogenesis and differentiation, with the aim of uncovering the basis for congenital heart defects. Benoit has recently become an editor for Development, and we asked him about his research and career and discussed how social media can help scientific progress.

When did you first become interested in developmental biology?

When I was in my third year of undergraduate studies at the University of Ottawa, I took a developmental biology course that had a research component. The university had an axolotl colony, so we did all sorts of classic experiments, such as grafting Spemann organisers. I totally fell in love with developmental biology. However, when I asked the teaching assistant what it took to become a developmental biologist he wasn’t very motivating. He said you had to spend 6 years in graduate school, then postdoc for a number of years, then find a job that doesn’t pay well and fight for grants; I shelved that idea and instead had thoughts of medical school. Then a plant genetics research project the following year got me interested in genetics, and I ended up doing a PhD in physiology, looking at heart gene expression.

Developmental biology took a back seat for several years, but during my PhD I found myself reading lots of developmental biology papers, as well as papers on transcriptional regulation. These got me thinking about how great it would be to understand how gene expression is regulated in development. When I was doing my postdoc with Jon and Christine Seidman they discovered that the gene encoding the T-box transcription factor TBX5 was the mutated gene in Holt-Oram syndrome, which includes congenital heart defects. They asked me whether I wanted to make the Tbx5 knockout mouse, model the disease and understand its function. Right there I saw the opportunity for putting together everything that I had always dreamed of doing in one project. I wasn’t in a developmental biology lab but it seemed like I was embarking on a project in that field, and I was fortunate to be surrounded by developmental biology labs, such as those run by Cliff Tabin, Norbert Perrimon and Connie Cepko. Simply by osmosis, by doing and talking constantly about developmental biology over the years, I immersed myself in it.

Why did you decide to focus your research on the heart?

My graduate work was on cardiac physiology, and I joined the Seidman lab so that I could make mouse models of cardiomyopathies. I always had an interest in the heart because of heart disease in the family. When I started out, one might have said that if I wanted to study heart disease I should have been studying heart attacks and atherosclerosis. Now, it is obvious that if we really want to fix hearts after a heart attack, we need to be able to build new heart cells, and that is what developmental biology is all about. This has actually become a reality, and I have been fortunate to participate in some of those discoveries.

What are the projects your lab is working on at the moment?

An important clinical motivation for our research is to understand the basis for congenital heart defects. I am really excited because we are finally able to do things in a way and on a scale that I had always dreamt of. We want to understand all the genomic switches and regulators that are involved in cardiac lineage determination and cardiac differentiation. We are taking a strategic approach by focusing on certain chromatin remodellers and DNA-binding transcription factors that we know are involved. We are also using new approaches to understand gene regulation during differentiation: for example, investigating the 3D interactions in the genome that shape or control these regulatory events.

We have really migrated from investigating a single gene at a time to addressing what is actually happening at the genome level: what is interacting with what, and how is that important? With the advent of new genomic and engineering technologies, such as TALENs (transcription activator-like effector nucleases) and CRISPRs (clustered regularly interspaced short palindromic repeats), the sky is the limit. For example, it took me 2 years of my postdoc to make the Tbx5 mutation, but a new postdoc in my lab generated the same mutation in 3 weeks. This means we can now address the function of regulatory elements not just in a heterologous context or in an artificial assay, but in a differentiating cell and, as we work on mouse, in a differentiating organism. Ultimately, the goal is to get a genomic blueprint of cardiac differentiation.

How stem cell research fits within developmental biology is a much-discussed topic. Your work is at the crossroads between these two fields: where do you stand in this discussion?

Yesterday someone referred to me as a ‘stem cell guy’, which is funny because we have really only published one and half stem cell-related papers! I’ve had this discussion with the lab recently: do we have a lab identity, and does it matter? Are we a stem cell lab now? Are we still a heart development lab? Or are we a transcription/chromatin lab that happens to be studying that molecular process in the developing heart? Our conclusion was that we are all of those things. We don’t need to pigeon-hole ourselves, because stem cells are a part of developmental biology. We want to understand progenitor allocation, morphogenesis, and how cells behave from the point of view of gene regulation. Our research topic allows us to be stem cell scientists, developmental biologists and chromatin biologists. I have had people join my lab with a background in developmental biology who are now doing primarily stem cell-based differentiation projects or chromatin-based projects, and vice versa. We incorporate all of their different skill sets and approaches, and I have fantastic people in the lab who can keep track of all the techniques and approaches. I hope we are uncategorisable!

Did you have a mentor or someone who inspired you during your career?

There are two people who have been major influences on my career. One of them is Janet Rossant and the other is Eric Olson. They have both been enthusiastic supporters of my science, which is really important. When you are starting out you don’t know if what you are doing is actually any good or if it will be appreciated, and I got really wonderful encouragement from both of them. I sought and got fantastic career advice from Janet very early on, when I was still a postdoc, and afterwards when I moved to Toronto. She has been a very good career mentor, and a generous colleague. Eric was an influence scientifically. I have got to know him over the years and the way he does things is tremendously inspiring. After I hear Eric give a talk I have two immediate reactions. The first is that I might as well quit science, because I will never be able to achieve something as impressive. But the stronger reaction is to be really motivated to go where I didn’t think I would be able to go, and go there without any fear.

How have you found your first months as a Development editor?

It is a tremendous honour. Development has always been one of my favourite journals and to be an editor among all the current and former editors who are the giants of developmental biology is humbling and a great honour. One of my goals is to try to help the journal increase its visibility and broaden its scope. In a way, the journal has already been doing this quite successfully with the recent Stem Cells and Regeneration section. I also want to encourage those colleagues in my field who are not contributing so much anymore to come back to the journal and those that are newer to consider sending their best stuff in. The history and the prestige behind Development is apparent to most but is not appreciated by many. That is what I would like to be able to bring to my role as editor.

Is there any particular type of paper, or particular topics, that you would like to see people submitting to Development?

I would like people who work on stem cell models of differentiation to think of the journal as a good place for their papers. I would also like to see more people who are doing very high quality molecular embryology to send their best work to the journal. There’s more competition now in the journal sphere, and I think Development has one of the most important places. However, we need to continue persuading people to send what they consider their best work to the journal. We will do that by accepting the best papers and by submitting our own best papers.

You are a very active user of Twitter, but many scientists see social media as a waste of time. Why do you use Twitter, and do you think scientists should be more active on social media?

Most scientists aren’t aware of the advantages of using Twitter. People wonder why it is interesting to know what someone had for lunch, or where they are going every minute, but that is not what Twitter is about. Twitter for me has been a really important source of information. I have been able to have real-time scientific discussions from my living room with people across the four corners of the world – mini conversations that I would not necessarily have otherwise had. I also get to know about some of the science that people are doing, especially in the genomics field, which has embraced Twitter as a means of communication. Of course, there are a lot of general views and amusing things that are nice to know about, but I see it more as a global science communication tool. You are also able to interact and get people’s opinions in a really immediate way. Sometimes people are overly frank on Twitter, which can be a bad thing; but it can also be nice: you really get to know what people are thinking, as opposed to just reading their work. I’m enthusiastic about Twitter, and I tell people about it, but I try not to beat them over the head with the gospel of Twitter. It’s not for everyone.

What would people be surprised to find out about you?

Despite being Canadian I didn’t live much of my childhood in Canada. My father was a diplomat, so I have lived in a number of different countries across the world. I was born in Tel Aviv, and I was baptised in the ancient monastery of Latrun, which only very rarely (every 50 years or so) has baptisms.

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Here are the highlights from the current issue of Development:

Profiling the mammalian brain

In mammals, adult neurogenesis is highly restricted to the subventricular zone and to the subgranular zone (SGZ) of the hippocampal dentate gyrus. Is neurogenesis in these regions a recapitulation of developmental neural production, or does it involve distinct molecular and cellular processes? And are these processes conserved across mammalian species? To help answer these questions, Ed Lein and colleagues (p. 4633) have performed a detailed expression profiling analysis of the SGZ in adult mice and in developing and adult rhesus macaques. Their datasets suggest that the SGZ niche is highly heterogeneous, with enrichment for markers of various progenitor and differentiated cell types. These results also identify a large set of genes enriched in the SGZ of both species, many of which are also well known to be involved in developmental neurogenesis, suggesting a conserved programme operating during development and in adulthood. Together, these data provide a valuable resource for the community and highlight key factors for neurogenesis in both mice and monkeys.

No auxin gradient in the gametophyte

The female gametes of flowering plants are produced within a structure known as the gametophyte, which develops inside the carpel of the flower. The female gametophyte (FG) contains several cell types, and it has been proposed that their fate is specified, according to position, by an internal auxin gradient. Ueli Grossniklaus and co-workers (p. 4544) set out to model this proposed auxin gradient in silico, to understand better how it might regulate fate determination. Using physiologically plausible parameters, they found that only very shallow auxin gradients could be maintained, which were unlikely to allow robust patterning of the FG, suggesting that cell fate may not be defined by an auxin gradient. Indeed, more detailed examination of auxin patterns suggested that no such gradient exists in either Arabidopsis or maize. Instead, dynamic auxin signals could be observed in surrounding sporophytic tissues, and the authors propose that auxin may act indirectly in the sporophyte rather than directly in the FG to control FG cell fate.

Guiding mDA neurons

Although much is known about the specification and differentiation of midbrain dopaminergic (mDA) neurons, the mechanisms regulating their migration within the ventral midbrain (VM) are poorly understood. Migration of several other neuronal types is under the control of CXCL12/CXCR4 signalling, which has been shown to impact on migration, neuritogenesis and axonal pathfinding. Now, Ernest Arenas and colleagues (p. 4554) set out to investigate whether this chemokine pathway might also regulate mDA neuron migration. They find that Cxcl12 is expressed in the meninges surrounding the VM, whereas the Cxcr4 receptor is expressed in the mDA neurons and their precursors. Using both in vitro culture and in vivo approaches, the authors show that mDA neurons migrate towards the meningeal source of CXCL12, in a Cxcr4-dependent manner; importantly, in Cxcr4 mutant embryos, mDA neurons are misplaced. Moreover, neuritogenesis of these neurons is impaired when CXCL12/CXCR4 signalling is perturbed. Together, these results reveal a key role for this chemokine pathway in the regulation of mDA neuron migration.

Stem cells need escorts

Stem cell renewal in vivo often requires a specialised microenvironment, the stem cell niche. Niche cells provide self-renewal signals as well as structural and spatial cues to regulate stem cell maintenance and differentiation. Here, Pankaj Sahai-Hernandez and Todd Nystul (p. 4490) investigate the follicle stem cell (FSC) niche of the Drosophila ovary, providing evidence that the escort cells of the germarium – which surround germline cysts and support their development – are also key for FSC maintenance. Hedgehog (Hh) and Wingless (Wg) pathways are known to promote FSC self-renewal, and the distant terminal filament and cap cells were proposed to be the sources for these signals. However, the authors here show that escort cells are the essential source of Wg for FSC function, whereas Hh is produced from multiple somatic cell types – including escort cells – and acts on both FSCs and their progeny. Moreover, escort cells contact FSCs and likely provide a dynamic niche for their maintenance, revealing a new component of the niche and a new function for escort cells.

A new twist on Hox in the limb

Hox genes provide positional information along both the body’s anterior-posterior and the limb’s proximal-distal axes. Analysis of Hox gene function in the limb has primarily focussed on their roles in skeletal patterning. Now, Deneen Wellik and co-workers (p. 4574) find that Hox11 genes are most strongly expressed in the connective tissue of the developing mouse limb, rather than the skeletal elements. Moreover, Hoxa11/Hoxd11 mutants show severe defects in tendon and muscle patterning in addition to their well-characterised role in patterning the skeleton. All defects are confined to the zeugopod region where Hox11 is known to function. These phenotypes do not appear to be a consequence of skeletal malformation, as compound mutants with a single functional Hox11 allele show no defects in the skeleton, but display significant disruption of tendons and muscles. These results define a previously unappreciated function for Hox genes in the limb, and suggest that they may act regionally to coordinate development of the various tissues of the musculoskeletal system.

Egg arrest: a tale of two phosphatases

Before fertilization, animal eggs are maintained in cell cycle arrest, to prevent parthenogenetic activation. In vertebrates, this is achieved by MAPK- and Emi2-mediated inhibition of the anaphase promoting complex/cyclosome (APC/C). Sperm induce egg activation by calcium-dependent activation of CaMKII, which triggers the destruction of Emi2, activating APC/C. However, invertebrates do not possess an Emi2 homologue, raising the question of how egg activation is achieved in these species. On p. 4583, Alex McDougall and colleagues address this problem in ascidians, the closest relatives to the vertebrates. They find no role for CaMKII, but show that the phosphatase calcineurin (CN) is required, acting to promote APC/C activity. Moreover, basal activity of the phosphatase PP2A is also essential for full APC/C function and egg activation. As CN is involved in egg activation in Drosophila, and plays an auxiliary role in Xenopus, the authors suggest that this may represent the ancestral mechanism of egg activation, which has been lost in mammals and replaced by a CaMKII-dependent pathway.

PLUS…

The cell biology of mammalian fertilization

Despite numerous studies, the molecular mechanisms underpinning the fertilization event in mammals remain largely unknown. However, as summarized here by Masuru Okabe, recent work using both gene-manipulated animals and in vitro studies has begun to elucidate essential sperm and egg molecules and to establish predictive models of successful fertilization. See the Primer on p. 4471

Left-right asymmetry: lessons from Cancún

The satellite symposium on ‘Making and breaking the left-right axis: implications of laterality in development and disease’ was held in June 2013 in conjunction with the 17th ISDB meeting in Cancún, Mexico. As summarized by Rebecca Burdine and Tamara Caspary, leaders in the field gathered at the symposium to discuss recent advances in understanding how left-right asymmetry is generated and utilized across the animal kingdom. See the Meeting Review on p. 4465

An interview with Benoit Bruneau

Benoit Bruneau is a developmental biologist based at the Gladstone Institutes in San Francisco. His lab studies the transcription factors and chromatin remodelling complexes that regulate cardiac organogenesis and differentiation, with the aim of uncovering the basis for congenital heart defects. Benoit has recently become an editor for Development, and we asked him about his research and career and discussed how social media can help scientific progress. See the Spotlight article on p. 4463

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Greetings, Node readers! We at The University of Chicago have just resumed our yearly Development, Regeneration and Stem Cell Biology Journal Club. I would like to take this opportunity to thank this year’s student organizer, Steve Briscoe. Steve is a 3rd year student in the DRSB program and a member of Dr. Cliff Ragsdale’s laboratory. He is already doing an excellent job arranging speakers and making sure refreshments are provided (keeping both students and faculty happy). Thanks, Steve! This month’s post comes from our very first meeting, in which we discussed Xiong et al.’s recent paper Specified Neural Progenitors Sort to Form Sharp Domains after Noisy SHH Signaling (Cell. Vol. 153, Issue 3, 25 April 2013, Pages 550-561). 

Morphogens hold a special place in the heart of developmental biologists. Hated by some, frustrating many, attracting countless others, morphogens have captivated scholars for many years. The beauty of the morphogen lies in its ability to create complex patterns, which often have both structural and functional significance. These patterns frequently appear as sharp delineations of cell types in a developing tissue.

The classic model of how such specific patterns can form is described in Lewis Wolpert’s “French flag” model (1969). Imagine a gradient of a diffusible morphogen across a field of unspecified cells, drawn as large blank rectangles (fig. 1). As the morphogen diffuses from source to sink, the concentration of the signal drops, creating a gradient from high to low concentration. Within this gradient, there are threshold concentrations to which cells can respond. The fate of each cell is determined by its position in the signaling field; that is, which threshold concentration the cell encounters. A cell receiving a high concentration of the morphogen will respond differently from a cell receiving a low concentration of the morphogen, creating a spatial pattern, such as the three broad stripes of the French flag (fig. 1).

However, to create the sharp boundaries of cell types seen in embryos, this model relies on precise signal responses at stable cell locations. But, as we all know, development is a messy business. Cells in developing tissues are not typically sitting still; rather, they undergo complex movement, migration, division, and death. How can a clear pattern come from this chaos? Xiong et al. (2013) provide a possible answer as to how sharp boundaries of cell types form in a dynamic, growing tissue.

An excellent example of such a tissue can be found in the vertebral neural tube, in which sharply defined progenitor domains form along the dorsal-ventral axis. It is thought that cells in the neural tube respond to a ventral-to-dorsal gradient of Sonic Hedgehog (SHH), entering a specific state of gene expression relative to the SHH levels encountered. At this point, intracellular gene regulatory network interactions between SHH-related transcription factors establish discrete cell fates, which are no longer dependent on SHH signaling (Xiong et al. 2013 and reverences therein). Again, however, we are faced with an important question. How can cells receive such precise spatial and temporal cues when they are moving and proliferating?

Using a new imaging platform they term “in toto imaging” of zebrafish, Xiong et al. investigated the neural tube in more detail. They not only analyzed the pattern of cell specification, but also investigated the migration trajectories of the neural tube progenitors. Instead of the expected “French flag-style” separation of specified progenitor cells, the researchers discovered that cells with different fates were spatially mixed in the developing neural tube (fig. 2). Thus, there seem to be heterogeneous signaling responses to SHH in the neural tube. The authors also show that the cells are sorted out into discrete domains based on their fate (fig 2), although how this task is accomplished is yet unknown.

Overall, it seems that cell sorting acts to correct the imprecision of a gradient-system with noisy inductive signals in a dynamic tissue (fig. 3). Many have pondered the morphogen gradient, wondering how such a system could really function in the embryonic milieu. With this study, we have another way to consider the way in which precise, beautiful and functional patterns are enacted in dynamic tissues. Exciting future work in other classic morphogen-gradient systems will determine whether this is an isolated case or a widely-spread phenomenon.

This post was composed by Haley K. Stinnett, PhD Candidate in the department of Organismal Biology and Anatomy at the University of Chicago. 

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The Node was full of activity in October. Here are some of the highlights!

New series

– ‘A day in the life’ is our new series on the model organisms used in developmental biology. Check out the current posts already available:

   A day in the life of a Xenopus lab

   A day in the life of a zebrafish lab

   A day in the life of a mouse lab

   A day in the life of a Drosophila lab

– As if one series was not enough, we also launched a series on Science Outreach, which we hope will highlight interesting projects out there, as well as few easy activities you may want to try. Check out our first case studies: Science outreach in music festivals, the EMBL programme bridging the gap between labs and schools, how to combine music, art and performance to talk about Evo Devo, and what it is like to participate in ‘I’m a scientist, get me out of here!’. Also have a look at our two first activities- speed dating with scientists and explaining protein folding.

Meeting reports

– The students who attended the 13th FASEB Plant Biology conference on ‘Mechanisms in Plant Development’ wrote about the meeting.

– Francesca reposted her article for the BSDB newsletter about the BSDB meeting on Axon Guidance and Regeneration.

– Steve and Alexandra wrote about attending the Company of Biologists workshop on the evolution of the human neocortex, while Katherine reported on the associated public talk at the Royal Society.

– and we summarised some coming meeting deadlines that you might want to put in your diary.

Research

– This month’s Stem Cell Beauty post is on a Cell Stem Cell paper where Andoniadou and colleagues identify a pool of stem cells in the adult pituitary gland.

– A recent paper by the Benitah lab (IRB Barcelona) described the daily cyclic activity of the genes in skin stem cells, and how disruption of this cyclical activity has implications for disease.

Also on the Node

– We interviewed mouse and stem cell developmental biologist and current ISSCR president Janet Rossant.

– Ewart wrote a literary interpretation of cellular reprogramming.

– and Thomas posted an opinion piece where he considered what may be wrong with the current structure of science.
 
 
Happy Reading!

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The Wellcome Trust – Medical Research Council Stem Cell Institute draws together outstanding researchers from 25 stem cell laboratories in Cambridge to form a world-leading centre for stem cell biology and medicine. The Institute receives core funding from the Wellcome Trust and Medical Research Council and is also a University Strategic Initiative. This generous support is enabling the Institute to expand and build on its reputation for excellence in this cutting-edge field.
Principal Technician

Salary: £33,230 – £44,607pa

The funds for this post are available until 30th June 2017 in the first instance.
We are now commencing an exciting period of change as we prepare for the design and build of 800m2 of new accommodation on the University’s Biomedical Campus. The role holder will be key in assisting the Administrator to both maintain and improve existing infrastructure but also, and vitally, in supporting and assisting with relocation design and planning. After the relocation, planned for 2017, the role holder will maintain and strengthen the core services as well as having input into their strategic planning.

To assist the Institute Administrator in the day-to-day running of the Institute the key aspects of the role are: Leadership, Communication and Problem Solving.

The role holder will be responsible for building maintenance and security, implementation Health and Safety procedures, and organisation and supervision of the Institute’s technical and cleaning staff.  Experience in managing building projects and refurbishments is desirable.

You should be able to demonstrate experience in recruitment, supervision and performance management and will have excellent written and oral communication skills.  You will be responsible for procurement and purchasing of high value goods and services and must have a good understanding of financial accounting processes. Practical experience of computerised accounting packages and familiarity with University Financial System is desirable but training can be provided.

Educated to degree level or equivalent in a biological science or related subject, you will have previous management experience in a senior post in a science-related area in either higher education or industry setting as well as excellent motivational and interpersonal skills. Extensive experience in a biomedical environment including a period of hands on research is essential.

The building is multi-occupancy building and you will act as the Safety Officer for the Stem Cell Institute and the Cambridge Systems Biology Centre and will liaise with the Department of Chemical Engineering and Biotechnology in all matters relating to building maintenance.

To apply, please visit our vacancies webpage:

http://www.stemcells.cam.ac.uk/careers-study/vacancies/

Informal enquiries are also welcome via email: cscrjobs@cscr.cam.ac.uk

Applications must be submitted by 17:00 on the closing date of 28^th November 2013.

Previous applicants do not need to apply.

Interviews will be held in the afternoon of Wednesday 18^th December 2013. If you have not been invited for interview by Wednesday 11^th December 2013, you have not been successful on this occasion.

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At EuroStemCell we’ve been watching The Node’s outreach series with interest. It’s really great to see public engagement featured ike this!

Meanwhile, we’ve been beavering away on all kinds of activities, which you can find out more about in our October Newsletter, just out last night. There’s lots to celebrate this month – we launched 5 new language versions of our film ‘Stem cells – the future‘ and it’s now also available to order on DVD; we held an event showcasing our writing competition winners; and, hot off the presses, our partner Elena Cattaneo has been awarded Stem Cell Person of the Year 2013 for all her wonderful work in science, public engagement and policy.

As usual, there’s also plenty of great new reading material on stem cells on our website, from Christele Gonneau’s latest image blog (also published on The Node in more specialist form) to an interview with Connie Eaves and a review of Paul Knoepfler’s new book, Stem Cells: An Insider’s Guide.

Stem cells – the future, le futur, die Zukunft, il futuro, nasza przyszłość, el futuro

We’re excited to announce that our short film, Stem cells – the future: an introduction to iPS cells, is now available in French, German, Italian, Polish and Spanish as well as English, with a supporting quiz for the classroom. You can order a DVD or view the film online and download the quiz, all in your language. Read more

Elena Cattaneo is Stem Cell Person of the Year!

Many congratulations to our partner, Dr Elena Cattaneo, who is the winner of the 2013 Stem Cell Person of the Year Award run by Dr Paul Knoepfler via his well-known blog. We know Elena not only as a leading scientist, but also as a very active, fantastically energetic and supportive collaborator in public engagement with stem cell research. She’s also recently become a senator. All in all, a great choice for Stem Cell Person of the Year!

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‘‘None of the scientists would comment on the record, for fear that it would affect their funding or that of their postdocs and graduate students’’ Nature, September 2012

‘Is science wrong?’ The Economist, frontcover October 2013

A Disclaimer

I have been very fortunate to come across senior scientists in my career who do not correspond to the stereotype that I put forward below; quite the opposite. I would thus like to make it clear that this piece is not at all aimed at any particular individuals. It is simply a hypothesis as to why science is, or might be, wrong.

A hypothesis

The first quote above comes from a news article that accompanied the publication last year of the findings of the ENCODE project consortium, and was part of Nature’s coverage of the project that included a mini-discussion of the (now seemingly) age-old debate about the merits of funding large consortia vs. investigator-led, hypothesis-driven research.

It came back to me recently as I was pondering a podcast from that most esteemed of journalistic news sources, The Economist. In their 2012 review of the year, they (correctly in my view) called the ENCODE publications (there were 30 papers published across 3 journals: Nature, Genome Research and Genome Biology) ‘‘the most significant findings of 2012 in life science’’. Now, in late 2013, they have run a piece, and indeed a front cover, entitled ‘‘Is science wrong?’’. This new discussion examines not the philosophical underpinnings of the scientific method in its modern incarnation, as might be concluded from the title (and front cover); rather, they bring to light a debate that until now has, I think, been largely brushed under the carpet by the scientific establishment. It is one that the huge army of excellent scientists either having been previously, or likely to be in future, forced out of science have long been airing. Perhaps now that someone other than the disenfranchised have made the point, funding agencies and their government paymasters, not to mention senior scientists, will begin to listen.

The criticism boils down, ultimately, to a single contention: that the modern career structure in science contradicts the very aims of science itself. Journals don’t publish repetitions of previous work, funders won’t fund it, and guess what? Scientists won’t do it. Cue massive surprise and outrage when significant proportions of published work are not repeatable. If you recruit some of the brightest people on the planet whose only way to remain doing what they love is to play a system that pits them against each other in an incredibly rudimentary way, then you cannot act surprised and outraged when they play that system to the detriment of the scientific enterprise.

A significant problem exists within the scientific community, however, that perpetuates this wrong: no one who in a position of power seems prepared to change it. To say that science attracts egos is something of an obvious statement to anyone who has ever met a scientist (or read one of their blogs), let alone been to a scientific conference and seen them talk about their work. The scientific career structure at present does not simply allow self-promotion, it absolutely depends upon it. That this is not in the interests of science as a discipline (and of course the future generations of the world who will depend upon its activity for their technology) should be self-evident to anyone with a brain, let alone the superb education of those at the top of the scientific establishment.

However, if the people who get to the top of science have been rigorously selected for their ability for self-promotion, then those same people are very unlikely to set about systematically re-designing the system for the better. It is rather depressingly reminiscent of a careers session that I heard of recently where some young female PhD students were quizzing a (very) leading light of the scientific world about career planning. ‘Families are not an option’ was the gist of the response from the luminary. She was female. A woman who feels she has had to give up the very notion of family life in order to get where she is surely is less likely to advise young women coming after her that they should be entitled to have both career and family. I may be wrong – I am certainly not a scientific luminary, let alone a woman – but I suspect that I am not.

Science shouldn’t be like this. Surely, we actually do know better. So should funders. Some lone voices have been saying this for years and years. Perhaps now some journalists have cottoned on to it, somebody with power will actually listen. It is, quite literally, not rocket science.

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My name is Nana and I’m a third year PhD student at the MRC National Institute for Medical Research in London. Our lab is in the Division of Molecular Neurobiology—so it comes as no surprise that we work on the brain! All animals need a functional brain to interpret sensory information and to produce behavioural responses. In the brain, a large diversity of cell types, neurons and glial cells, form complicated networks. We are interested in how neurons and glia are generated, and how neurons can form specific connections with each other. These connections are formed in a stepwise coordinated manner, and our model to study neural circuit assembly is the visual system of the fruit fly, Drosophila melanogaster.

Cartoon of a Drosophila male (left) and female (right). From Shimosako et al. doi:10.1007/978-1-62703-655-9_4

The Drosophila visual system, as its vertebrate counterpart, is organised into synaptic units of columns and layers. These are not only important for visual information processing, but also during development make it easier for each neuron to find its partner. I, in particular, am investigating how neurons target their axons and dendrites into specific layers in the brain.

My model organism, Drosophila melanogaster, is a small fly weighing about 1mg. The life cycle of flies is very short, and the embryo develops into an adult in 10 days at 25 °C. This is great because you know the outcome of experiments relatively quickly, compared to animals with longer life cycles.  Flies live in tubes containing fly food at the bottom. Fly food consists of cornmeal, yeast, and other nutrients they need. The flies will lay eggs on the food, the hatched larvae will eat through the food, and eventually crawl up the side of the tube to pupate. After about 4 days, those flies hatch, and the whole cycle continues.

A fly vial. Larvae and adults eat the food at the bottom, where eggs are also laid. Larvae crawl up the wall when they’re ready to pupate, and a few days later, adults hatch.

Most “fly people” start their day in the fly room. It’s a temperature controlled room, maintained at 22 °C, with workstations consisting of dissecting microscopes and fly pads. Fly pads release a controlled amount of CO₂, so the flies placed on the pads fall asleep. It’s absolutely essential to have this, otherwise we won’t be able to sort through the flies if they’re still moving! We have two other rooms with different temperatures—18 °C and 25 °C. Those don’t have workstations, but are used to keep our fly stocks. The life cycle of flies varies depending on the temperature, and it gets shorter as the temperature increases. The 18 °C room is for stocks which we don’t use on a daily basis, but need to keep for future experiments. 25 °C is the temperature we most frequently use for experiments. Flies are happy at 25 °C, they lay eggs well, and the timing of development is well characterised so we know precisely what happens at certain time points. For example, we know when the embryos hatch, the larvae moult, and when the pigments become visible in the eyes and wings of pupae. Not only can we see these external features, but we also know where the axons of well-studied neurons are at particular developmental stages.

A typical fly workstation, with a microscope, CO₂ pad and a CO₂ “gun”, which we use to insert CO₂ directly into vials so flies fall asleep.

In the fly room, we first collect “virgins”. Virgins are females that have never mated with males, and we need these for genetic crosses. To ensure that the females are virgins, we collect them within a few hours of their hatching before they are developed enough to mate. And since most flies hatch in the morning, we’re most likely to find virgins when we first get to work. Once we have enough virgins, and depending on when we need the offspring for an experiment, we set up the crosses. To set up a cross, we simply retrieve the males and virgins of the right genotype from their vials, and move them to a new vial. The males then proceed to court the females within minutes.

Flies are asleep on the CO₂ pad, so we can select the virgins (near the front).

After collecting virgins, I usually move on to dissections. The cells of the visual system are generated from the third instar larval stage onwards, and continue to develop throughout pupal stages. Since my neurons of choice target their axons in late pupal development, most dissections I do are of pupae. I need to stage the pupae, meaning I collect the white prepupae, which have freshly-pupated and still retain the larval white colour, and count the number of hours after puparium formation (APF). The white prepupal stage corresponds to 0 hours APF, and the flies hatch between 90-100 hours. I look at anything between 24 and 85 hours APF depending on the experiment. We dissect fly brains under a microscope, using a tweezer in each hand. The great thing about flies is that the number of samples you can dissect is not limited by any laws or rules. The only factor which limits the sample number is how difficult it is to get progeny of crosses with the right genotype—when the flies have multiple transgenes loaded onto most of their chromosomes, they are not as healthy as wild type and sometimes refuse to hatch!

WPP are collected on a plate with agar containing grape juice. They’re very small, as you can see compared to the pencil.

The best thing about using Drosophila is its extensive genetic toolbox. Using the Gal4-UAS system, we can express any transgene in specific cell types. Additional genetic “tricks” allow us to label neurons or glia of interest in the brain, also at a single cell level. This is very useful when we want to investigate the function of genes, and for example would like to know whether they’re required in a specific cell. Another advantage of flies is that the genome is completely sequenced. We have good knowledge of the sequence of all genes often down to the single base. There are some un-annotated (potential) genes in the genome, and there’s always excitement if you work on them—because if you find a function for them, you get to pick the name of the gene. I think fly gene names are really inventive and fun, which help you remember them. swiss cheese, sex-lethal, technical knockout, and tinman to name a few!

After dissecting, I take care of my fly stocks before lunch. One annoying thing about flies is that we can’t cryopreserve the embryos, so we always need to maintain stocks as live flies. This means we need to “flip stocks” every few weeks, which involves transferring the flies from their old tube to a new tube.

At lunchtime, all the fly groups eat together. There are three fly labs at NIMR, with around 30 people in total. We all share the fly room and equipment, and give experimental advice to each other. I see everyone every day in the fly room and in the canteen, and we certainly build amazing friendships. I’d say that’s a perk of working in a communal fly environment!

The countryside view from the NIMR canteen.

The first thing I do in the afternoon is to incubate my dissected brain samples from the previous day in secondary antibody. They would have been incubated in primary antibody overnight, and after 2.5 hours incubation in secondary antibody at room temperature, they are good to go.

To prepare the brains for confocal microscopy, I mount them on a glass slide. We don’t slice the brains, but look at them as a whole because they are very small. We place the tiny brains in a drop of mounting medium, and then under a fluorescence dissecting microscope, shift their orientation in the medium. This gives us the perfect orientation to visualise the brain in a reproducible manner, but it requires a lot of patience, and your hands need to learn to make adjustments in the μm range. It’s essential to get this right, otherwise we won’t be able to tell whether axon projections are reaching the correct area of the brain. And we need to know if it’s a phenotype, or just looks like one because it’s sloppily mounted!
 

A typical set up of a confocal microscope.

The confocal microscope is arguably the most important thing our lab uses. We need to look at fluorescently labelled neurons at the single cell level so it’s crucial to have a microscope with high enough resolution. We use techniques which allow us to label our cells with sometimes up to 5 different colours in the same sample, so generating an image (with multiple focal planes) could take a long time. The current microscope we have is only a few years old, and is able to do fast scans. Even then, when I have to follow the neuronal processes across the brain, scans could take about an hour. Still, it is very rewarding to look at the final image, which labels neurons (or antibodies recognising proteins) in different colours.

A rainbow in the fly visual system. We use a technique called Flybow to identify individual neurons in the Drosophila optic lobe. Left: Timofeev et al. 2012; Right: from D. Hadjieconomou.

The final thing I do before calling it a day is to go to the fly room and collect virgins again. This time I collect the flies that have hatched during the day. Then I store my flies at 18 °C for the evening, and after a night’s rest, they will be ready for me again in the morning.

It’s been 3 years and 8 months since I started working in my current lab. I started off as a research technician, focussing on molecular biology projects to create new transgenic fly lines. Now, I’m fully immersed in the fly genetics and immunohistochemistry—and looking forward to continue working with these cool little guys to find out more about brain development.

This post is part of a series on a day in the life of developmental biology labs working on different model organisms. You can read the introduction to the series here and read other posts in this series here.

(16 votes)

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