Applications are invited from highly motivated and enthusiastic individuals for a BBSRC DTP funded PhD position in the laboratory of Dr. Raman Das at the Faculty of Biology, Medicine and Health at the University of Manchester. This position will commence in September 2017.
This project builds on our recent discovery of a new form of cell sub-division (apical abscission) that regulates shedding of the apical tips of newborn neurons, leading to an acute loss of cell polarity (Das and Storey, Science, 2014). How these neurons re-establish their polarity and subsequently extend an axon in the correct orientation is now a key question in the field. This project will focus on the role of the apical Par polarity complex in re-establishment of polarity in the new-born neuron using a highly interdisciplinary approach integrating pioneering cell and developmental biology techniques with powerful quantitative Mass Spectrometry-based proteomics. The successful candidate will utilise cutting-edge live-tissue imaging techniques complemented by super-resolution microscopy to visualise the fine cellular architecture of differentiating neurons. Quantitative proteomics approaches will then be employed to identify novel molecular determinants that influence neuron repolarisation.
Overall, this highly interdisciplinary project represents an ideal opportunity for advanced training in modern cell and developmental biology techniques. As this project lies at the critical interface between cell and developmental biology it is therefore also likely to provide physiologically relevant insights into the molecular mechanisms leading to neuron polarisation and axon extension.
The Francis Crick Institute is a new discovery biomedical research institute in central London. We are core-funded by Cancer Research UK, the UK Medical Research Council, and the Wellcome Trust and partnered by Imperial College, King’s College and University College London.
We are recruiting enthusiastic and motivated early career researchers who wish to set up their first independent research programme at the Crick in any area of biomedicine. We welcome applications from those who wish to work on a flexible and/or part-time basis.
Successful candidates will be offered a competitive salary with a 6-year contract, renewable once for a total of 12 years. The institute will provide fully equipped laboratory space and access to core-funded state-of-the-art technology facilities. Salaries and consumables for around five people, including graduate students, will be provided. Research groups will have the opportunity to expand further based on external grants.
The Crick will provide mentoring and support to ensure its early career Group Leaders make the most of their time at the institute and develop a world-class research programme. Towards the end of the 12-year period we will support them to find leadership positions elsewhere, with potential for a transition start-up package for those remaining in the UK.
Applications from candidates with a PhD and postdoctoral experience should be submitted online at:
Two years ago, Development held a meeting on the emerging field of stem cells and human development. In announcing the meeting, the organisers described a knowledge gap:
“Strikingly, although we understand intimate details of the development of a broad range of vertebrate and invertebrate species, we know almost nothing about the development of the human embryo beyond morphological descriptions”
But times are changing. We can now shed light on some of the black boxes of human development, thanks to the controlled differentiation of embryonic or induced pluripotent stem cells (iPSCs), the coaxing of self-organisation in organoids, new ways to culture early human embryos at the implantation stage, and the availability of human foetal material to which in vitro generated tissues can be compared.
As well as helping us understand our origins, these technical advances provide an opportunity for clinical understanding and therapeutics, particularly with the capacity to derive stem cells from patients, and the relative ease of gene editing using CRISPR. iPSCs also circumvent many of the ethical issues and socio-political controversies that surround embryo-derived stem cells. All these features have come together to make it an exciting and fast-moving time for human developmental biology.
The Southbridge Hotel & Conference Centre, site of the 2016 meeting.
Following the success of the 2014 meeting, a second event was held last month in Southbridge, a small Massachusetts town once known as the ‘Eye of the Commonwealth’ for its history of manufacturing optical products. The meeting was held on the site of the American Optical Company factory, an employer of thousands before it shut down in the eighties, and the social was held in the Optical Heritage Museum. It was fitting to see so much beautiful light microscopy during the talks.
An exhibit at the Optical Heritage Museum
The attendees came from across the globe and ranged from early PhD students to institute directors. Their research covered various aspects of human development, from the earliest fate choices in the blastocyst to the formation of mature organs. In keeping with the meeting’s title, almost all the speakers described how they were making use of human pluripotent stem cells, and many of the talks covered particulars of the speaker’s in house differentiation protocol. But it wasn’t just a methods fest, as a lot of fascinating biology comes out of the process of differentiation or self-organisation itself. Plus, as Ali Brivanlou’s talk reminded us, descriptive human embryology is still in its infancy, particularly for the stages immediately following implantation, so there is much to learn with observation alone.
The coffee and drinks breaks were buzzing hives of discussion
Opening the meeting, Azim Surani set the tone for many of the talks by emphasising the distinctions between human and mouse primordial germ cells, which are specified by different genetic networks. The more we look at human development, the more differences with mice emerge. Perhaps we shouldn’t be surprised by this – after all, it’s been many millions of years since we last shared a common ancestor – but it does raise the question of how much knowledge really is transferrable from mouse to human, and of the place of non-human models in the future.
According to many of the speakers, you needn’t mothball your animal house just yet: animal models offer a vital complement to human stem cell or organoid work. For instance, mice provide an environment in which to transplant human cells and assay their developmental, and indeed clinical, potential. This was shown for neuromesodermal progenitors by Anestis Tsakiridis, liver organoids by Takanori Takebe, chondrocytes by April Craft, dopaminergic neurons by Lorenz Studer, and cortical cells by Pierre Vanderhaeghen. As Jason Spence remarked, the current field is based on decades of model organism work, and working out the differences is one side of the story; integrating human cell work with established animal models is another.
The panel discussion on translation to the clinic. From L-R: Lorenz Studer, Guy Sauvageau, Yann Barrandon and Sally Temple.
Another recurrent theme of the meeting was how the basic insights gained from studying human tissues can help patients. In a panel discussion session, we heard from four researchers currently translating stem cell biology into treatments. Lorenz Studer told us about the assault course of regulation at each step of the process (though he cautioned against complaining too much: these treatments need to be safe, and to work), Guy Sauvageau discussed how scaling up the production of cells to clinically useful quantities requires the involvement of good bioengineers from the start, and Sally Temple spoke about the interesting science that resulted from the concerns of the regulators. Yann Barrandon reminded the audience that once you take the step to commercialise, you’re in another world; your cells become a product, and you have to prove that your product is not only effective, but will make money.
Just considering the stakeholders involved – public funders, venture capitalists, patient groups, patients themselves, research scientists in academic or commercial environments, biotech companies, spinoffs, university IP offices, government regulators – you get a feel for the challenge these scientists face, keeping in mind that their ultimate goal is always to improve the life of the patient, whether they suffer from neurodegeneration, hematologic diseases or severe skin burns.
Benoit Bruneau remarked from the audience that it was so novel and refreshing to be in a room full of developmental biologists talking about intellectual property, profit margins and clinical trials. Given the expansion of human stem cell work into every tissue of the body, each with its own inherent flaws, it seemed an apt time for the panel to give us a feel for how applied biology actually works.
Beer and coffee in the Tavern
As for the rest of the meeting: the poster sessions were well attended, and sites of lively and stimulating conversations. The pool tables and dartboards were well used at night (even giving some of us respite from the Clinton-Trump debate). And the social: local craft beer, a trip around the museum with Dick the curator, and local coffee in the tavern. Not your typical conference social!
Look out for a full report from the 2016 meeting in an upcoming issue of Development. In the meantime, you can read a report from the 2014 workshop by Alexander Medvinsky and Rick Livesey here, and also find Development’s 2015 Special Issue on human development here.
As an alternative to this mini-report, check out the story of the meeting as recorded on Twitter:
We are looking for an enthusiastic and highly motivated Staff Scientist or experienced Research Assistant/Technician to join the stem cell and regenerative medicine-based laboratory of Dr. April Craft, within the department of Orthopaedic Research at Boston Children’s Hospital and Harvard Medical School. Our lab studies the development of musculoskeletal tissues, primarily articular cartilage, using human pluripotent stem cells as a model system. Projects in the lab range from basic to translational research.
The candidate will be essentially involved in all aspects of the laboratory but will primarily focus on 1-2 prioritized scientific projects, including modeling of cartilage disorders using patient specific iPSCs. The successful candidate will work closely with the PI and post-doctoral fellows in the lab, and be responsible for maintaining human pluripotent stem cell differentiation cultures and analyzing/recording results using various established assays. Individualized research projects will be available based on proven experience and independence. Additional tasks include preparation of reagents and media, and a supporting role in lab supplies inventory/ordering and maintenance of lab equipment. Occasional weekend work is required. This job has physical requirements that include the ability to bend, lift and carry objects weighing up to 50 lbs on occasion, frequently reach and grasp objects above and below shoulder level, and occasional proofreading and checking documents for accuracy.
The applicant must be a US citizen or permanent resident. Applicants must have at least a BS/BA in Biomedical science (or equivalent); Candidates that have a MS or PhD degree are preferred. Applicants must have at least three years of cell culture experience, preferentially human embryonic stem cell culture, and a strong understanding of molecular biology. We will teach the right candidate the necessary skills. Salary will commensurate with experience. Excellent organization skills and communications skills in English are required. A minimum three-year commitment is requested, however this position is potentially long term.
Applicants should email a CV, contact information for three referees and a cover letter describing their background to april.craft@childrens.harvard.edu.
We are looking for an outstanding, highly motivated postdoctoral fellow to join our innovative young department in the stem cell and regenerative medicine-focused laboratory of Dr. April Craft, Assistant Professor of Orthopaedic Surgery at Boston Children’s Hospital and Harvard Medical School. Our lab studies the development of musculoskeletal tissues, primarily cartilage, using human and mouse embryonic (ESCs) and induced pluripotent stem cells (iPSCs) as a model system. Available projects in the lab range from basic developmental biology to translational research. We are interested in applying our knowledge of how to generate cartilage tissues from pluripotent stem cells to further understand how genetic mutations cause skeletal dysplasias in patients, particularly those for which animal models do not exist. We have also recently identified a panel of molecular markers that may help to define progenitor cells that are best suited for cartilage regeneration and repair.
A strong background in one of the following fields is required: pluripotent stem cell biology, basic developmental biology, or musculoskeletal/cartilage development, homeostasis or disease. Candidates with hands on experience using pluripotent stem cells will be given preferential consideration. The successful candidate will have a recently acquired PhD or MD-PhD, a minimum of 3 years laboratory experience including tissue culture, and at least one first author publication. The candidate must be a US citizen or permanent resident, and must possess excellent communication & writing skills in English. Members of the Craft lab participate in seminar series and other events within the Harvard Stem Cell and Regenerative Biology Program, Boston Children’s Hospital Orthopaedic Research Laboratories, Harvard Stem Cell Institute, and Harvard Medical School.
Applicants should email a CV, contact information for three referees and a cover letter describing their background and research interests to april.craft@childrens.harvard.edu.
A Ph.D. position in molecular cell and developmental biology of plants is available in the lab of Prof. Kay Schneitz, Dept. of Plant Developmental Biology, Technical University of Munich in Freising/Germany. The successful candidate will work on the molecular characterization of the signaling pathway mediated by the atypical transmembrane receptor-like kinase STRUBBELIG (SUB) in Arabidopsis (1-4). The SUB pathway functionally links intercellular signaling controlled by receptor kinases and plasmodesmata, gateable channels interconnecting most plant cells, during tissue morphogenesis of for example flowers and ovules. Starting date is negotiable but ideally the position should be filled as soon as possible. The lab is part of the Collaborative Research Centre SFB924 (sfb924.wzw.tum.de) and thus funding comes from the German Research Council (DFG) and is at the usual EG13/2 level. Requirements are e.g. a German masters (with a mark of 2.5 or better), a French DEA (a final average of 13 or more), or a masters thesis. The person needs to have a firm basis in basic molecular techniques. Fluency in English is a must. Freising is located about 35 km to the north of Munich. Munich is a lively, cosmopolitan city close to beautiful lakes and the Alps. For further information please contact Kay Schneitz (kay.schneitz@tum.de) and visit the webpage (plantdev.wzw.tum.de).
(1) Chevalier et.al. 2005 PNAS 103: 9074-9079.
(2) Fulton et.al. 2009 PLoS Genetics 5: e1000355
(3) Vaddepalli et.al. 2011 PLoS One 6: e19730
(4) Vaddepalli et.al. 2014 Development 141: 4139-4148
In an interview, Lewis Cantley, Director of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, talked about discovering the PI3K pathway and the relationship between metabolism and cancer
Chunhui Xu and colleagues presented a human iPSC model for catecholaminergic polymorphic ventricular tachycardia.
Katherine Swenson-Fields and colleagues described a pathway for the differentiation of macrophages in polycistic kidney disease.
We are seeking a creative and exceptionally motivated candidate to fill a post-doctoral position in the field of evolutionary and developmental genetics.
Research in the Kamberov lab is directed at uncovering the genetic basis of human adaptive traits, with a core focus on the evolution of skin appendages, namely sweat glands and hair follicles. In this pursuit, we utilize a highly interdisciplinary approach that combines mouse and human genetics with developmental biology and evolutionary genomics. The culmination of this research program is to not only enhance the understanding of human evolution but also to apply what we have learned in translational efforts that lead to the improvement of human health and alleviation of disease, particularly in the context of skin and skin appendage regeneration.
Projects include:
-Dissection of molecular pathways underlying skin appendage development and evolution.
-High throughput screening for regulatory elements controlling the specification and patterning of hair follicles and sweat glands.
-Dissection of stem cell populations in the skin and the regeneration of human skin appendages in vitro.
-Discovery and functional modeling of evolutionarily significant human variants using comparative genomics and humanized mouse models.
The position provides an exciting opportunity to work at the interface of basic and translational research in a collaborative and stimulating environment, and gain experience in a diverse set of technical approaches at the cutting edge of evolutionary, developmental and regenerative biology.
A doctorate in biology or related field is required. Applicants with a strong background in developmental biology, genetics, genomics or molecular biology are encouraged to apply. Prior experience with mouse genetics and husbandry is preferred.
Interested candidates should provide: 1) a CV 2) a brief letter detailing your interest in the lab and relevant past research experience 3) contact information for three references who can comment on your research. Application materials and any questions regarding the position should be addressed to Yana Kamberov: yana2@mail.med.upenn.edu
We are currently seeking an independent and motivated scientist to join the research group led by Dr Anestis Tsakiridis (https://www.sheffield.ac.uk/cscb/tsakiridis). His work focuses on dissecting the molecular basis of cell fate decisions in the developing embryo and aims to exploit this knowledge for disease-modelling and regenerative medicine applications. The group is particularly interested in the biology of neuromesodermal progenitors (NMPs), the bipotent cell population which drives embryonic axis elongation by generating spinal cord neuroectoderm and paraxial mesoderm.
We have recently described the efficient derivation of NMPs from human pluripotent stem cells (hPSCs) thus establishing a tractable system for studying these progenitors in vitro. The ideal candidate will employ this model in combination with various screens and complementary approaches aiming to define the intrinsic and extrinsic determinants of NMP maintenance and differentiation. Applicants should hold a PhD in a related field and have experience in hPSC culture/differentiation, immunocytochemistry, high content imaging and chromatin immunoprecipitation. A background in Crispr/Cas9-based genome editing and/or bioinformatics would be highly advantageous.
September was notable for the amount of new jobs posted, from Kansas to Copenhagen to King’s College London, and PhD to tenure-track. Check out our jobs page for the latest opportunities. In case you missed them, here are some of our other monthly highlights:
We continued our ‘People behind the papers’ series with Adam Johnston, who talked about his recent work on mouse digit tip regeneration and his new lab in Canada. We also featured an interview with Lewis Cantley from Disease Models and Mechanisms.
Life beyond the bench
A visual report from the Royal Society early career conference by Scriberian