Technology is quickly changing many parts of medicine, giving people more power to take charge of their health care. Taking isotope labeled peptides as an example, stable isotope labeled peptides have been widely applied in the nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). The combination of SIL peptides with NMR spectroscopy allow for the incorporation of NMR active nuclei which can reduce the complexity of spectra, and then help researchers to obtain novel correlations between atoms for more structural information.
Technology has changed people’s daily life to a large degree. In current days, people can use smartphones to track their blood sugar. And in future days, apps and accessories may be available to check cholesterol or track the heart’s electrical activity. Instead of the doctor’s office or lab, people could soon be showing up for checkups with the info already in hand, gathering information about their health. In addition to the use of new technologies, there are also some other parts of health care where doctors and patients agreed, such as the use of genetic testing for diagnose problems.
Against the backdrop of health care reform and a controversial medical device tax, medical technology companies are focusing more than ever on products that deliver cheaper, faster, more efficient patient care. Many in the industry like Isotope Labeling process have long felt overly burdened by what they consider to be an unnecessarily complex approval process. In fact, modern medical technology has achieved great success in a variety of fields, including cancer diagnosis, clinical application, experimental advance and the like, which could bring safe and effective medical devices to market more quickly and at a lower cost. For example, Melanoma Biopsies, as a huge number of dangerous-looking mole, it has been used as a handheld tool for multispectral analysis of tissue morphology.
Clearly, there are also some other aspects should be considered, such as the efficiency, side effects, etc. Investigation and research of modern medical technology ethics under the guidance of the concept of scientific development could be extremely necessary. Medical and health services to achieve long-term development, health care facilities, medical technology and health security has been significantly improved. While the development of healthcare facility is always in a dynamic process because of the influence of medical needs, medical technology, healthcare system, and other unpredictable factors. And for companies that sell medical technology, the arrival of the digital hospital has signalled a new era. Thus, maybe Integrilin can attract increasing attention in life sciences groups.
Along with the social economy prosperity and medical technology advances, medical ethics has made brilliant achievements, but currently still face a predicament in the course of development. In other words, medical technology advance not only means the medicine but also the medical spirit.
As you may have seen, we at Development have recently announced a change to our peer review process, introducing a cross-referee commenting step. This should be in place within the next week or two, and we’re hoping it will help us to make better decisions on papers, and to make the revision process easier for authors.
We were approached by Retraction Watch, who regularly run features on various aspects of publishing, about this initiative, and they’ve just posted my interview with them. So if you’re interested in finding out more about what we’re doing and why, or want to see how I’ve managed to squeeze chocolate and wine into a Q&A about peer review, please head on over to Retraction Watch for the full interview! Obviously I’m happy to answer any other questions you might have about this process, so just leave any comments or queries below, or in the RW comments feed.
And we’ll be monitoring how well this initiative works, so I expect you’ll be hearing more from me about this once we’ve had a chance to review the process and look at its impact on the papers we handle…
Changes in body organ morphology have allowed animals to better exploit diverse habitats. As organ morphology is under genetic control, genetic modifications provide the basis for the wide range of morphologies. However, as our knowledge of the genetic basis of phenotypic diversification in evolution has focused mostly on quantitative traits, it is not clear how simple genetic changes can give rise to modified functional organs. The paper by the groups of Jordi Casanova at IRB Barcelona and IBMB, and Xavier Franch-Marro at IBE and has addressed this issue by analysing the expression and function of regulatory genes in the developing tracheal systems of two insect species.
The larval tracheal system of Drosophila can be distinguished from the less derived tracheal system of the beetle Tribolium by two main features. First, Tribolium has lateral spiracles connecting the trachea to the exterior in each segment, while Drosophila has only one pair of posterior spiracles. Second, Drosophila, but not Tribolium, has two prominent longitudinal branches that distribute air from the posterior spiracles. Both innovations, although affecting different structures, are functionally dependent on each other and linked to habitat occupancy. Thus, Drosophila larvae buried in semi-liquid environments keep their posterior spiracles above the surface and distribute the air along the body via the dorsal trunks. Conversely, the lateral spiracles of free-living Tribolium larvae provide sufficient airflow to all segments, thereby making the formation of thick dorsal trunks unnecessary.
The work published in Development shows that the acquisition of each innovation is associated with change in the expression domains of individual transcription factors, spalt and cut, respectively. However, the two genetic modifications are connected both functionally and genetically, thus providing an evolutionary scenario to account for the coordinated evolution of functionally interrelated structures.
Department/Location: Wellcome Trust – Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, UK.
Salary: £25,023-£28,982
Reference: PS10184
Closing date: 17 October 2016
Fixed-term: The funds for this post are available until 30 June 2017 in the first instance.
The Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute is an international centre of excellence for stem cell research and regenerative medicine. Scientists in the Institute collaborate to advance our knowledge of various stem cell types and to perform pioneering work in translational research areas, providing the foundation for new medical treatments. The Institute currently comprises 29 research groups based across 6 sites in Cambridge. In 2018 all researchers will move to a new building on the Cambridge Biomedical Campus.
Applications are invited for a computational biologist to join the SCI’s bioinformatics group. We apply state-of-the-art experimental and computational methods toward understanding the biological properties and biomedical potential of stem cells.
The vacant post is at Research Assistant level and would be suitable for individuals with either a computational or biological background. The post holder will bridge the research groups within the SCI and will analyse next generation sequencing data using cutting edge software tools on internally (SCI)-produced data. He/she will work in a team of bioinformaticians dedicated to the application of modern bioinformatics techniques to stem cell research.
Candidates should be able to work in a UNIX/Linux environment. Proficiency with a scripting language (e.g. Perl/Python) and statistical data analysis tools (R, Matlab) would be a strong advantage. Additional experience with analysis of high-throughput sequencing data is desirable. The post holder will be involved in the development and interpretation of multilayer genomic, transcriptomic and epigenomic data. Necessary training in specialist computational tools will be provided; the main criterion is an enthusiasm to use bioinformatic approaches to advance stem cell research.
To apply online for this vacancy and to view further information about the role, please visit: http://www.jobs.cam.ac.uk/job/11530. This will take you to the role on the University’s Job Opportunities pages. There you will need to click on the ‘Apply online’ button and register an account with the University’s Web Recruitment System (if you have not already) and log in before completing the online application form.
Please upload your Curriculum Vitae (CV) and a covering letter in the Upload section of the online application to supplement your application. If you upload any additional documents which have not been requested, we will not be able to consider these as part of your application.
The closing date for all applications is the Monday 17 October 2016.
Informal enquiries are also welcome via email to: jobs@stemcells.cam.ac.uk.
Interviews will be held towards the end of October 2016.
Please quote reference PS10184 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.
DMM is looking for an enthusiastic intern who wishes to gain experience in science publishing, including writing press releases, contributing to our social media activities, and supporting our Reviews Editor with commissioned articles. The internship is envisaged to last for up to 1 year at a salary of £15,000 p.a.
Our interns have a great track record of continuing on into important publishing roles.
Joining an experienced and successful team, the internship offers an ideal opportunity to gain in-depth experience on a growing Open Access journal in the exciting and fast-moving field of translational research. DMM publishes primary research articles and a well-regarded front section, including commissioned reviews and poster articles, thought-provoking editorials and interviews with leaders in the field. We also have an active social media presence and will be growing our press release programme. The intern will work alongside an established publishing team in our Cambridge offices.
Because the journal serves both basic biomedical researchers and clinicians, applicants will have a PhD or MD, ideally with some relevant research experience, and a broad knowledge of model organisms and disease issues.
Is the role for you? You would be expected to…
Support our Reviews Editor:
• Identify and commission topical front-section content from top-ranking scientists, see articles through peer review and work closely with authors to finalise articles for publication.
• Travel to international scientific conferences and research institutes, representing the journal, keeping abreast of the latest research and making contacts in the DMM community.
Develop your own areas of activity:
• Spot newsworthy articles, write informative press releases and handle any media enquiries.
• Interview high-profile scientists in the biomedical arena.
• Contribute to our social media output.
• Be creative – contribute other ideas for the journal’s development and promotion.
Essential requirements for the job are enthusiasm, commitment, judgement and integrity. Candidates should have excellent interpersonal skills and confidence, excellent oral and written communication skills, and a broad interest in research and the research community. They should also be willing to travel. Previous editorial experience is not required, but we would expect candidates to be able to demonstrate an interest in scientific communication.
A post-doctoral position is available in the Franz-Odendaal Bone Development Lab to study the developmental basis of the vertebrate ocular skeleton in a comparative context. Highly motivated and independent individuals with excellent interpersonal skills are encouraged to apply. The successful applicant will take a key role in our research program which interests spans evo-devo, developmental genetics and phenotypic variation.
We are seeking a recent doctoral student in Biological Sciences or related fields with experience in Molecular Biology, Cell and Developmental Biology. Experience with zebrafish and/or chick embryos is desirable but not required. Opportunities to supervise students will be available.
Please send curriculum vitae and summary of research interests via email.
Dr Tamara Franz-Odendaal
Franz-Odendaal Bone Development Lab
Mount Saint Vincent University,
Halifax, Nova Scotia, Canada
We are offering a Research Assistant position funded by a Wellcome Investigator Award. The successful candidate for this position will perform experiments and provide technical support in the group of James Briscoe. The group studies the molecular and cellular mechanisms responsible for the embryonic development of the vertebrate nervous system.
performing research projects involving molecular biology, tissue culture and embryological techniques
providing technical advice and teaching basic techniques to new members
interacting with colleagues by discussing results and techniques and ideas for improvements
overseeing the effective running of the lab by monitoring stock levels and ordering consumables and reagents, maintaining equipment, databases and methods sheets.
The Francis Crick Institute (the Crick) is a registered charity whose purpose is to conduct biomedical research into all aspects of human health and disease. Dedicated to research excellence, the institute will be a world-leading centre of biomedical research and innovation. The Crick is located in a new, purpose-built research centre in central London (next to St Pancras International), housing 1,250 researchers and 250 support staff.
The new Program in Functional and Chemical Genomics at the Oklahoma Medical Research Foundation (OMRF, http://omrf.org/) is inviting applications for multiple independent faculty positions at the Assistant and Associate Member levels (Assistant or Associate Professor equivalent). OMRF is a non-profit private foundation dedicated to fundamental, interdisciplinary research and to the translation of knowledge to medicine and public health in areas including autoimmune disease, cardiovascular disease, aging-related diseases, metabolic diseases and cancer. The Program will combine the latest technologies in genomics, functional genomics, model systems biology, chemical biology and computational analyses to tackle fundamental questions emerging from ongoing high-throughput genetic and epigenetic studies of disease. The Program occupies newly renovated space designed to foster highly collaborative and innovative research using computational and/or genetic models systems such as yeast, C. elegans, Drosophila, zebrafish, mice and stem cells aimed at scaling the evaluation of genetic and epigenetic alterations. This biological understanding will be used to interrogate opportunities for therapeutic intervention and define chemical mechanisms. Faculty research programs at OMRF are supported by competitive start-up and salary packages, as well as, ongoing annual support and a commitment to faculty development. OMRF faculty have access to state-of-the-art mouse and zebrafish facilities and outstanding core technology laboratories like Flow Cytometry, Imaging, NextGen Sequencing and more.
We are looking for interactive and creative faculty whose research interests synergize with, but expand, the Foundation’s current research expertise. Candidates holding a Ph.D. and/or M.D. in biological or biomedical science fields, with relevant postdoctoral experience, and outstanding research accomplishments in areas including, but not limited to the following are invited to apply immediately:
• Functional Genomics using Genetic Model Systems
• Drug Target Validation and Chemical Screening
• Stem and Progenitor Cell Biology
• Cell Fating and Developmental Biology
• Genetics and Epigenetics Interactions
• Systems Biology
Successful candidates are expected to develop and maintain robust extramurally funded research programs and may seek adjunct appointments in one of the many relevant University of Oklahoma School of Medicine and/or Graduate College Departments, and will have opportunities to participate in one or more graduate student education programs.
To apply, submit the following documents via FunctionalChemicalGenomics@omrf.org : 1) Cover Letter; 2) Curriculum Vitae; 3) Research Statement; 4) Contact information for 3 references.
We are seeking outstanding candidates to lead a project studying Notch, TGF-β, and ephrinB2 signaling pathways in arterial venous programming/reprogramming and the implication in development and diseases. We take a conditional mouse genetic approach to manipulating gene expression in endothelial cell-specific and temporally controlled fashion. We also use cutting-edge in vivo real time imaging technology, including an in-lab constructed two-photon microscope, which provides exceptional access to gene function in vivo at the cellular resolution along with blood flow measurement overtime in live animals. This basic approach is complemented by preclinical studies with our elegant mouse models of diseases, offering outstanding opportunities for translational research. The laboratory is well equipped with state-of-the-art capabilities at the molecular, cellular, and organismic levels. In addition to funding from the PI, we also have an excellent track record in sponsoring postdoc fellowships. We are interested in a well-trained and well-published recent Ph.D. graduates to continue our innovative breakthroughs in a rewarding training program. This postdoctoral research is an excellent platform for a highly productive Ph.D. with a strong motivation to become a future group leader. Experience with mouse techniques is a plus. UCSF offers outstanding postdoctoral career development opportunities. Please submit your CV, research interests, and the names of three references by email with a subject title “postdoc application” to:
Rong Wang, Ph. D.
Professor
UCSF
rongwangucsf@gmail.com
For additional information visit:
http://profiles.ucsf.edu/rong.wang
http://wanglab.surgery.ucsf.edu
https://bms.ucsf.edu/directory/faculty/rong-wang-phd
Each of us has around 6 pints of blood. The blood contains a number of different types of cells, including oxygen-transporting red blood cells, disease-protecting white blood cells or wound-closing platelets. But have you ever wondered where they all come from?
Quite amazingly, all these very different blood cells originate from the same parental cell, called the haematopoietic stem cell (HSC for short). HSCs live inside our bone marrow and keep making new blood cells throughout life. That’s why you don’t have to worry if you cut yourself and lose some blood – your bone marrow will make new cells very quickly. In fact, a single haematopoietic stem cell has the potential to make all 6 pints of your blood!
As it turns out, the way we make the first HSCs is very similar to all other vertebrates studied so far (Ciau-Uitz et al, 2014): they come from endothelial cells, the cells lining the vessels of the circulatory system. But only a specialised type of endothelium gives rise to HSCs – the haemogenic endothelium, located in the main artery of the 6-week old human embryo. 100 years ago, Emmel had observed blood cells associated with arterial endothelium in pig embryos (Fig.1).
Figure 1 – Transversal section of the main artery (the dorsal aorta) of a pig embryo. Adapted from Emmel, 1916.
At that time, similar observations were made in a miriad of other vertebrate embryos, including the mongoose, the chick, the rabbit and the human (see Adamo and Garcia-Cardena, 2012 for the full references). This abundance of early observations led to the hypothesis that blood cells came from… blood vessels! The evidence to support this very simple hypothesis didn’t come until 2010, when a few research groups imaged the birth of an HSC in live zebrafish embryos (Bertrand et al., 2010; Kissa and Herbomel, 2010; Lam et al., 2010).
In the Patient lab, we use zebrafish to find out what makes these endothelial cells, already part of a differentiated tissue, become our all-important HSCs. In our recent Developmental Cell paper, we solved another piece of the puzzle: we showed that the cytokine Transforming Growth Factor β (TGFβ) is needed very early in the developing embryos to make the endothelium become haemogenic, so that it can make HSCs. Here is the story of how we got there.
Why TGFβ?
Any haematologist will tell you that if you give TGFβ to adult mice, their blood stem cells will stop proliferating and, if exposed for too long, they will die. So why would you need TGFβ to make the stem cells in the first place and why on Earth would you bother to even look at TGFβ? Well, the clue comes from epithelial cancers: an oncologist will tell you that TGFβ is a tumour suppressor that keeps cancer cells from proliferating and even from moving to other parts of the body…until it doesn’t! After a fatal tipping point, TGFβ becomes an oncogene and actually encourages the cancer cells to transform and go invade other tissues. This is what led us to look at TGFβ in the formation of HSCs – an endothelial cell leaving its place in a functional vessel and becoming an HSC (see Figure 2 for our own live imaging of the birth of an HSC) is remarkably similar to a metastasizing cancer cell!
Figure 2 – Confocal timelapse imaging of an emerging haematopoietic stem cell in the zebrafish dorsal aorta (yellow arrow)
This was a great opportunity to put together my interest in developmental biology and in stem cells, and hopefully contribute with new discoveries that may also be relevant to human biology. The first signs were encouraging: the TGFβ receptor tgfβR2 and its ligands tgfβ1a and tgfβ1b were present in the main embryonic artery at the right time; we also found tgfβ2 and tgfβ3 in the neighbouring notochord, further suggesting TGFβ signalling might play a role. Knocking down the receptor indeed led to the loss of haematopoietic cells, so we were in business! I convinced the British Heart Foundation that TGFβ was a good idea and got an Intermediate Fellowship to go ahead with this line of research, hosted in the Patient lab at the MRC Weatherall Institute of Molecular Medicine. You can find out more about other research ongoing at the MRC WIMM on the WIMM blog.
The first pieces of the puzzle
After we demonstrated that TGFβ was required to make the HSCs, we wanted to figure out how it related to other pathways known to play a role in the process. We turned to NanoString technology, a neat multiplex hybridization technology to look at what happened to gene expression downstream of TGFβ. Of the 100 plus genes we looked at, one turned out to be activated by TGFβ – the Notch ligand jag1a. This was a crucial finding, because jag1 had already been described as a target of TGFβ in metastasizing cancer cells (Zavadil et al., 2004) and so the link to Notch signalling was already established. We followed this lead and discovered that switching off jag1a also resulted in losing HSCs. Moreover, forced expression of jag1a rescued the loss of HSCs in TGFβ-deficient embryos, further supporting the TGFβ-Notch link.
Through a series of experiments that involved switching off other important cell signalling pathways and subsequent gene expression analysis, we managed to place the TGFβ pathway downstream of VEGF – a signal that is a well known player in the development of blood and blood vessels.
The final piece
At this point, we were excited that we had a nice VEGF-TGFβ-Notch story to tell, but we were not finished yet! We wanted to see which of the TGFβ ligands was doing the job. There are a number of different family members (TGFβ1, TGFβ2, TGFβ3), all of which trigger very similar events in their target cells. To our surprise, not only our prime suspects (based on expression analysis), TGFβ1a and b were required, but also TGFβ3 played a role. Even more surprisingly, TGFβ3 was more important at a later stage, when the HSCs actually leave the endothelium and become motile. Sticking to the similarities with cancer, this would be when the cancer cells metastasize. In short, while TGFβ1 and TGFβ3 were required to make the HSCs, they came from different sources and were required at different times. This finding really puts emphasis on how important it is to consider the timing of events when studying embryonic development.
Is this the end of the story?
No!… This is really just the beginning. What we discovered is that there is a ‘window of opportunity’ where TGFβ is required, but we and others have shown that if you have too much TGFβ you will also struggle to make HSCs (Nimmo et al., 2013; Vargel et al., 2016; Yang et al., 2016). Think of this like you’re cooking a meal: when you add salt, too much or too little of it will ruin your dish, so it’s important to get it right. How can we reconcile both observations? Also, how does TGFβ3 ‘take over’ the role of the main TGFβ ligand and how is it regulated? This is one of the most exciting times in the life of a researcher – when you get an answer that comes with… many more questions!
How can understanding the origins of our blood be useful in the long term? If we discover enough pieces of the puzzle, we may be able to write down a trusted ‘recipe’ to prepare the haematopoietic stem cells in a laboratory dish, step by step. Such optimised, lab-grown HSCs would have a great potential to help people suffering from various blood disorders, including leukaemias. Let’s hope we’ll be able to start ‘cooking’ soon!
Contributors: Rui Monteiro and Tomasz Dobrzycki
References
Adamo, L., and Garcia-Cardena, G. (2012). The vascular origin of hematopoietic cells. Dev Biol 362, 1-10.
Bertrand, J.Y., Chi, N.C., Santoso, B., Teng, S., Stainier, D.Y., and Traver, D. (2010). Haematopoietic stem cells derive directly from aortic endothelium during development. Nature 464, 108-111.
Kissa, K., and Herbomel, P. (2010). Blood stem cells emerge from aortic endothelium by a novel type of cell transition. Nature 464, 112-115.
Lam, E.Y., Hall, C.J., Crosier, P.S., Crosier, K.E., and Flores, M.V. (2010). Live imaging of Runx1 expression in the dorsal aorta tracks the emergence of blood progenitors from endothelial cells. Blood 116, 909-914.
Nimmo, R., Ciau-Uitz, A., Ruiz-Herguido, C., Soneji, S., Bigas, A., Patient, R., and Enver, T. (2013). MiR-142-3p controls the specification of definitive hemangioblasts during ontogeny. Dev Cell 26, 237-249.
Vargel, Ö., Zhang, Y., Kosim, K., Ganter, K., Foehr, S., Mardenborough, Y., Shvartsman, M., Enright, A.J., Krijgsveld, J., and Lancrin, C. (2016). Activation of the TGFβ pathway impairs endothelial to haematopoietic transition. Scientific reports 6, 21518.
Yang, Q., Liu, X., Zhou, T., Cook, J., Nguyen, K., and Bai, X. (2016). RNA polymerase II pausing differentially regulates signaling pathway genes to control hematopoietic stem cell emergence in zebrafish. Blood.
Zavadil, J., Cermak, L., Soto-Nieves, N., and Bottinger, E.P. (2004). Integration of TGF-beta/Smad and Jagged1/Notch signalling in epithelial-to-mesenchymal transition. EMBO J 23, 1155-1165.
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