A major challenge when studying the cell biological bases underlying morphogenesis is represented by the gap between the sub-cellular and the tissue-organ scale (Figure 1). Ideally, one would like to follow tissue dynamics with sub-cellular resolution and obtain ultra-structural details about the organization of specific plasma membrane domains, cytoskeletal structures, intracellular compartments and vesicular carriers involved in signaling and adhesion. It is, indeed, the spatio-temporal modulation of membrane and cytoskeletal dynamics in individual cells or group of cells, which ultimately drive tissue remodeling during organismal development. Cell shape changes play, indeed, a fundamental role during embryonic development and are often initiated by expansion or contraction of specific plasma membrane domains. While the role of the cytoskeleton in driving plasma membrane remodeling is well established, the contribution of membrane trafficking remains an open question.

Figure 1. Scales in developmental biology: from organisms (left panel, cross section of a Drosophila m. embryo ~0.5 mm) to organelles (right panel, endosome ~0.5 microns). Tissue and organ morphogenesis depends on the modulation of intracellular machines operating in the nanometer scale.

In my laboratory, for example, we are interested in understanding how endocytosis contributes to shaping cells and tissues during morphogenesis.  Although, the role of endocytosis in signaling and cell polarity is well-established, to what extent endocytosis is directly involved in shaping cells is less understood. The cellularization of the early Drosophila embryo provides an ideal system for studying the mechanisms driving plasma membrane remodeling during morphogenesis. Over the course of one hour a syncitium of 6000 nuclei is divided into an equal number of polarized epithelial cells by invagination and growth of the apical plasma membrane (for video see, http://youtu.be/kwN1aNAvTwk). Scanning electron microscopy studies revealed that during this process the apical plasma membrane undergoes a dramatic morphological re-organization characterized by the retraction of villous protrusions and flattening of the apical surface. To date, however, the apical surface of the embryo has proven extremely difficult to visualize in real time using traditional live imaging techniques.

In our recently published paper (Fabrowski P. et al 2013) we adapted Total Internal Reflection Microscopy (TIFR-M) to visualize endocytic dynamics during surface flattening in live Drosophila embryos. This microscopy technique relies upon an evanescent wave that exclusively illuminates a region in close proximity (10-200 nm) to the coverslip. In cell culture, TIRF-M has been successfully employed to visualize vesicle fission and fusion events with the plasma membrane (Toomre D. et al 2000). Furthermore, because of its high sensitivity and low signal to noise ratio, TIRF-M can be applied also to image single molecules dynamics (Jain A. et al 2012).

Imaging living organisms is not as simple as imaging single molecules in solution or cells grown on glass coverslips. In living organisms, such as developing embryos, cells move, are not adhering to coverslips and autofluorescence sometime poses a serious limit to the imaging techniques that can be employed. In the Drosophila embryo, cells are enclosed by the vitelline membrane and are surrounded by peri-vitelline fluid. The vitelline membrane is a proteinaceous waxy layer that tends to be autofluorescent when illuminated with blue (488) light. It seemed therefore unlikely that TIRF-M could be employed to visualize plasma membrane dynamics in live embryos.  However, after several failed attempts, we realized that it was possible to direct the laser light with such an angle that an evanescent wave could be generated at the interface between the vitelline membrane and the peri-vitelline fluid. This approach allowed us to visualize, for the first time, the morphogenetic remodeling of the apical surface over the entire course of cellularization (see movie below and  also movie S1 in Fabrowski P et al. 2013)

Quantification of endosome dynamics, marked by the small GTPase Rab5 tagged with GFP at its endogenous locus, revealed a massive increase in apical endocytosis that correlates with changes in apical morphology (Figure 2, for video see, http://youtu.be/9X5uM85lBBM).

Figure 2. TIRF-M imaging of apical endocytic dynamics during plasma membrane remodeling in live Drosophila embryo. From left to right, thee snapshots of early, middle and late stages of cellularization showing the up-regulation of endocytic vesicles marked by Rab5 (green). The plasma membrane is labeled by Gap-43 and it is shown in white. Scale bar, 10 microns.

In a series of experiments, which I will not describe here in detail, we demonstrated that endocytosis is required for surface flattening. We, therefore, decided to investigate the endocytic mechanisms driving this morphogenetic process. The large quantities of plasma membrane contained in protrusions together with the relative fast kinetics of flattening (~10 minutes) raised the question of whether clatrhrin coated vesicles mediated endocytosis could, by itself, be sufficient to drive membrane remodeling. To address this question, we employed Correlative Light-Electron Microscopy (CLEM), a powerful, but time-consuming technique, that allows one to correlate fluorescently labeled particles onto a corresponding electron microscope image. By combining CLEM with electron tomography we reconstructed the 3D organization of GFP labeled endocytic membranes. In summary, the results of this analysis revealed that surface flattening is driven by the activation of a prominent tubular endocytic pathway characterized by the formation of tubular plasma membrane invaginations that serve as platforms for the de novo generation of vacuolar Rab5-positive endosomes. Thus, surface flattening is an endocytosis dependent morphogenetic process during which endosomes form directly at the plasma membrane rather than by fusion of incoming clathrin coated vesicles.

In conclusions, the application of these powerful microscopy techniques to multicellular systems will undoubtedly help bridging the gap between the sub-cellular and the tissue-organ scale. The possibility, for example, of visualizing endocytic events during tissue differentiation should help characterizing the molecular regulation and spatial organization of signaling systems in an in vivo context with an unprecedented level of resolution.

References

Jain A, Liu R, Xiang YK, Ha T. (2012) Single-molecule pull-down for studying protein interactions Nat Protoc. 7(3), 445-52. doi: 10.1038/nprot.2011.452.

Toomre D, Steyer JA, Keller P, Almers W, Simons K. (2000) Fusion of constitutive membrane traffic with the cell surface observed by evanescent wave microscopy. J Cell Biol. 149 (1), 33-40.

Fabrowski P, Necakov AS, Mumbauer S, Loeser E, Reversi A, Streichan S, Briggs JA, De Renzis S. (2013) Tubular endocytosis drives remodelling of the apical surface during epithelial morphogenesis in Drosophila. Nat Commun.4:2244. doi: 10.1038/ncomms3244.

(6 votes)

Loading...

Novartis Institutes for Biomedical Research (NIBR) is a world leader in pharmaceutical research with a widely recognized culture for nurturing innovation and scientific excellence to address unmet medical needs. China NIBR based in Shanghai is dedicated to the research and development of products addressing diseases prevalent to China, and providing innovation in the understanding and curing of Epigenetic causes of diseases.

Cell fate specification and differentiation of stem cells into distinct cellular lineages during mouse embryogenesis are tightly regulated genetically and epigenetically, particularly via the interplay between key development regulators and various epigenetic modulations.  Such interaction and similar mechanisms are also manifested during regeneration and aging processes.  Epigenetic dysregulation will cause abnormal embryonic development and various human diseases.  To aid target discovery and mechanistic understanding of regeneration, we are inviting applications for an Investigator position in the regenerative medicine research group. The successful candidate will be part of the developmental biology core, focusing on novel target discovery and disease modeling for regenerative medicine.  He/She will be responsible for elucidating the roles of key epigenetic regulators during development and regeneration by using combinatory mouse genetics and epigenomic profiling approaches.   The successful candidate will also participate in multi- disciplinary drug discovery and development team to support target discovery in disease areas of focus.

minimum requirements:

• Ph.D. in Developmental Biology, Cell Biology or related fields, minimal three years postdoc training
• Hands-on experience with mouse embryology, histology or pathology analysis; familiar with key developmental pathways such as Wnt, BMP, Notch etc.
• Deep understanding of epigenetics and proficient in research technologies such as ChIP-Seq, and DNA methylation analysis are required. .
• Highly self-motivated and highly collaborative team worker is essential. Previously industrial experience is preferable.

Please send your resume to sarah.qi@novartis.com, thanks!

(No Ratings Yet)

Loading...

TED is a conference series of mostly amazing speakers across diverse fields in science, business, technology, culture, and global issues. They post tons of the talks on their website, www.ted.com, and not only do they have a full array of fascinating subject material, but they’re also a source of inspiration if you’re looking for ways to improve your presentation style or communicate with a broad audience.

Here is a round-up of 8 cool biology-themed talks to put on the next time you have a 5-20 minute incubation step.

1. Tyrone Hayes and Penelope Jagessar Chaffer: The toxic baby

A great collaboration between a filmmaker and frog biologist. They explore the chemicals in our environment and how these may be influencing human development and disease.

2. Munir Virani: Why I love vultures

A talk extolling the virtues of vultures, how they contribute to ecosystems and prevent the spread of disease, and the threats they face.

3. Cynthia Kenyon: Experiments that hint of longer lives

The story of a long-lived mutant in C. elegans, and the link between stress, metabolism, and lifespan.

4. Ellen Jorgensen: Biohacking — you can do it, too

Ellen Jorgensen is one of the founders of Genspace, a lab that teaches “regular people”  in the community to do molecular biology. She explains what they do (fun and interesting projects), and what they don’t do (create pathogens that will wipe out humanity).

5. Susan Lim: Transplant cells, not organs

Susan Lim highlights the problems with the current system of organ transplants, based on her moving personal experiences as a transplant surgeon in Singapore, and discusses her work on adipose stem cells.

6. Michael Dickinson: How a fly flies

A cool study of flight using model robot insects (!)

7. Emma Teeling: The secret of the bat genome

Emma Teeling is the Director of the Centre for Irish Bat Research, and discusses some of the unique biological features of bats, the rap bad they get in Western culture, and how they contribute to human agriculture, economics, and health.

8. Bonnie Bassler: How bacteria “talk”

Bacteria communicate for group behaviors like pathogenesis: Bonnie Bassler talks about the major advances made in her lab, with implications for all types of cell-cell communication.

(5 votes)

Loading...

As you may be aware, The Company of Biologists launched its own series of Workshops in 2010. Coming up this September is the workshop ‘Evolution of the human neocortex- how unique are we?’ Taking place at the beautiful Wiston House in Sussex, this workshop will bring together researchers from the fields of developmental and molecular biology, genetics and ethology to discuss our current view of human cortical evolution and what makes us unique.

The Company of Biologists’ Workshops are not just about facilitating the discussion of science between scientists, but also bringing that exciting science to the general public. This is why The Company of Biologists has organised an open lecture at the Royal Institution on Wednesday the 25th of September. This lecture is free and open to everyone, and will feature two of the researchers participating at the workshop. Svante Pääbo, from the Max Planck Institute for Evolutionary Anthropology will discuss his team’s work on the DNA of Neanderthals, while Arnold Kriegstein from the University of California San Francisco will discuss how the human brain compares with that of its close and distant relatives.

You can find more information on the workshop website and on the Royal Institution website.

The talk at the Royal Institution will take place on the 25^th of September. You can order your free ticket here.

Image from Wikimedia commons

(No Ratings Yet)

Loading...

For decades, the development of the early embryo and patterning of tissues has been studied with the help of a workhorse of developmental biology, the frog embryo.  Xenopus embryos are large and undergo clear morphological changes throughout their development that make them very quick and easy to work with in answering questions surrounding the formation of early germ layers and processes such as gastrulation.

However, a major disadvantage to working with Xenopus embryos is the amount of yolk contained within them.  Unlike in organisms such as zebrafish embryos, which have a separate yolk cell from which to draw their nutrition, the fertilised Xenopus embryo contains large yolk platelets, predominantly in the lower (vegetal) half of the embryo.  This yolk is primarily made up of the protein vitellogenin and can account for half of the protein content of the cell – a problem that has contributed to the somewhat lagging development of Xenopus mass spectrometry proteomics.  But the yolk also results in an opaque embryo that limits the options for imaging live embryos with light microscopy.  Mouse embryos are also opaque and so a method of imaging these embryos would be of great interest to many fields of developmental biology.

One approach to overcome this problem – published recently in Nature – has been developed at the Karlsruhe Institute of Technology by Jubin Kashev and Ralf Hofmann, with contributions from Xenopus embryos from the lab of Carole LaBonne.  This technique is phase-contrast X-ray tomography, using synchrotron radiation.

That sounds more complex than it is!  Regular X-ray imaging is typically carried out by firing X-rays at a subject and building up an image of tissues depending on how much they absorb X-rays.  However this is not at a good enough resolution for small samples such as Xenopus embryos, and requires a high blast of radiation and additionally injection of some sort of reagent to add contrast to the image.  This is where the synchrotron comes in.  This provides a coherent wave of radiation that is slowed through different tissues in a distinctive pattern at high resolution.  A series of 2D images is produced whilst the embryo is rotated and these 2D images are used to build up a 3D picture – this is the tomography part.

The researchers were able to control timing and duration of X-ray blasts to minimize damage to the embryo whilst capturing as much of the process of gastrulation as possible between stages 11.5 and 12.5 (the authors comment that a 2 hour window of development is reasonable to capture before damage to the embryo becomes a significant problem).  They found further evidence for the idea that the archenteron expands by uptake of external water; and also suggest previously unseen adhesive interactions occur between mesoendodermal cells, forming a ridge of contracted ectoderm at the point where dorsal and ventral mesendoderm meet and ectodermal cells begin to spread over the surface of the gastrula.  They suggest this structure may be destroyed in the traditional process of taking explants for further study, hence why it has not been observed prior to these studies.

The obvious limitation in this approach is the current availability of synchrotrons (in the Research Highlight in Nature, it is suggested that there are only 8 facilities in the world!).  But it is exactly this sort of innovation, at the frontiers of developmental biology and biophysics, which can help us overcome the traditional limitations to studies in developmental biology.

Beware of the Frog

References:

Moosmann, J. et al. X-ray phase-contrast in vivo microtomography probes new aspects of Xenopus gastrulation. Nature 497, 374–377 (2013).

Nawy, T. Embryos under the X-ray. Nature Methods 10, 603 (2013)

(7 votes)

Loading...

Turtles are firmly protected from predators by the unique bony shell. These animals are even capable to retract their head and limbs within the shell, thus their defense system seems to function perfectly. The turtle shell, in particular its dorsal part (carapace), is a strange structure, since it is contiguous with the ribs and vertebrae, unlike other armoured animals. How could such an invulnerable body plan ever evolve? Until recently, the mystery on the origin of the turtle shell has been invulnerable, as the protective nature of the shell itself.

To uncover the above question, our laboratory has been systematically working on the embryonic development of the turtle shell. Fortunately in Japan, soft-shelled turtles are cultivated for diets by many farmers, and thus we picked up the Chinise soft-shelled turtle (Pelodiscus sinensis) as an item for the research.

In every summer, our laboratory purchases hundreds of turtle eggs from the farmer. The eggs are covered with hard, mineralized shells, just like chicken eggs. But, unlike the latter, the turtle egg requires sufficient moisture, otherwise they become dried out soon. We therefore put the eggs on a pile of fully moistened peat moss, and place them in an incubator adjusted at 30ºC, so that a high rate of survival can be expected. The eggshell of the turtle is semitransparent, and embryonic blood vessels and eyes are visible through the shell, enabling us to identify the developmental stage before sampling.

The turtle research team in our laboratory consists of only a few members (in 2013, three postdocs), but explores multilayerd subjects from genomes to fossils. We are currently investigating detailed histology, and gene expressions presumably responsible for the origin of the shell. Simultaneously we visit museum collections from time to time to examine fossil skeletons (unlike the other members of the lab, I majored in vertebrate paleontology). Through these investigations, we recently elucidated that the major part of the carapace is derived purely from endoskeletal ribs.

Discussion in the turtle team often provides us with new insights, or hunches, which would potentially help us drive our researches forward. This interaction is, I believe, a key to uncovering the evolutionary process of the turtle shell, in near future.

Hirasawa, T., H. Nagashima, and S. Kuratani. 2013. The endoskeletal origin of the turtle carapace. Nature Communications 4:2107 DOI: 10.1038/ncomms3107

Another recent paper from our laboratory:

Wang et al., 2013. The draft genomes of soft-shell turtle and green sea turtle yield insights into the development and evolution of the turtle-specific body plan. Nature Genetics 45:701-706 DOI: 10.1038/Ng.2615

Animations show origins of the turtle carapace (RIKEN CDB):

http://www.cdb.riken.jp/en/05_development/0506_turtle01.html

(8 votes)

Loading...

How can a single fertilized egg become a full little human? It is because I wanted to answer that question that I became a scientist.

When I started my PhD studying the formation of blood stem cells during development,, I learnt how complex development was and how hard it was to address these questions. Though fun and rewarding, big challenges are also part of a scientist’s life. During the difficult times, there were two activities in particular that kept me motivated, confident and enthusiastic about science: 1) doing science outreach and 2) reading scientific publications to keep up to date with the field.

1) As for science outreach, I found it extremely rewarding and humbling to communicate science to non-scientists. It always made me feel proud to realize that I, as a scientist, play a very important role in society, especially given that I work in the controversial field of stem cells. Indeed, when I talk to non-scientists about stem cells, I feel that I contribute to their understanding of the strengths and weaknesses of the field and that, in the long run, it will help end all the misconceptions out there that are detrimental for both science and society.

2) Reading publications. First because they made me feel like I was part of a big worldwide enterprise and also because some of them were… well, quite artistic and beautiful…and like a good piece of art, some of these figures, pictures and graphical displays, were fascinating.

So, this is why I am very excited about writing this monthly blog. Each month, I will share with you the beauty of stem cells by selecting and commenting on a cool stem cell image from a publication, following a similar format to Erin Campbell’s previous posts. This monthly blog is a collaborative project between the Node and EuroStemCell, and therefore my posts will also be available on the EuroStemCell website (http://www.eurostemcell.org/stem-cell-images).

I will be posting my first stem cell image soon…

(5 votes)

Loading...

If you are a Twitter user you probably know that our Twitter account reports not only on Node posts, but also on other interesting news and content from around the internet. We don’t want the non-twitter users to miss out, so we have collated some of the most interesting (developmental) biology content that we found in the last month in one post.

News

– This month saw the first burger made in a lab from cow stem cells. Apparently not as tasty as the real deal!

– This year’s prestigious Royal Institution Christmas Lectures will be given by developmental biologist Allison Woolard!

– The first patient trial using iPS cells has started in Japan.

– And the first stem cells programmed using chemicals alone were reported.

Weird & wonderful

– Nobel Prize winners were given crayons and asked to sketch their research. This book is the result.

– An artistic biologist created a crocheted dissected mouse– an unusual theme for a cuddly toy?

– Do you love your science enough to write it in your skin? We spotted a website dedicated to science tattoos.

– Ever wanted to 3D print your favourite protein? The ASCB blog tells you how to do it.

Beautiful & Interesting Images

– This absolutely striking image of a zebrafish embryo was the Wellcome Trust Image of the month.

– Cambridge University has a very interesting playlist on their Youtube channel featuring beautiful microscopy images. Definitely worth a check!

– The University of Michigan has decided to use some of the beautiful images produced by their researchers to fund travel grants.

– The 23rd of July was Rosalind Franklin’s birthday, and this anniversary was celebrated with a very special google doodle:

Videos worth watching

– Trying to explain biology to non-scientists? We found a great animation by Stated Clearly that explains all your family needs to know about DNA, and this great introduction to Stem Cells by EuroStemCell.

– General Electrics recently hosted the 6 second science fair– a festival of 6 second movies about cool science. Not a lot of biology experiments, but definitely worth a look!

In the future we will be occasionally posting more interesting content found on the internet. If you don’t want to wait for these occasional posts, you can start following us on twitter @the_Node!

(3 votes)

Loading...

Symposium: The cell’s view of animal body plan evolution

Society for Integrative and Comparative Biology (SICB) Annual Meeting

January 3-7, 2014  Austin, TX

http://www.sicb.org/meetings/2014/symposia/cellevo.php

Abstract submission deadline: August 26 2013

http://www.sicb.org/meetings/2014/abstracts/

Registration deadline: November 9, 2013

Understanding how diverse animal body plans evolved remains one of the most exciting and challenging goals for evolutionary and developmental biologists alike. Over the past few decades, genomic and molecular genetic approaches have provided insights into which gene networks regulate cell fate specification.  It is less well understood how specification states launch specific cell biological properties, such as polarity, migration, and adhesion.  Yet, cells are the fundamental unit of all biological structures and phenomena – evolution shapes phenotypes by ultimately tinkering with cellular characteristics.  With recent advances in applying modern molecular, live-imaging, and modeling techniques to a broader range of experimental systems, can we now compare cell types across animal species to understand how they have mediated organismal evolution?  This symposium will bring together researchers who use varied approaches to test hypotheses at multiple levels of biological organization, ranging from systems-level studies of gene regulatory networks for cell behaviors to modeling cytoskeletal dynamics that drive tissue morphogenesis.

“Cellular Evolutionary Developmental Biology” does not exist as a codified field. Because of recent breakthroughs in research methods, this is the ideal time to discuss what it will look like in the near future. The diversity of expertise and perspectives present at the annual SICB meeting makes it an ideal venue to consider such an integrative topic. We hope that this symposium will stimulate a  synthesis that can inform new directions in the field in the future. The invited speaker symposium covers topics including cytoskeletal dynamics underlying patterning and morphogenesis of tissues, specification and gene regulatory networks leading to cellular behaviors and comparative cell biology of regeneration.

A poster session will follow this day long symposium. A complementary session of shorter contributed talks will be held on a different day. We encourage researchers to submit abstracts on a broad range of research topics pertaining to the evolution of development and developmental cell biology. We will select 10-15 short (15 minute) talks from submitted abstracts. We have a limited number of travel scholarships available to support the participation of students, postdoctoral researchers, and earl-career professors.

Make sure to select our symposium from the pull down menu when you submit your abstract (http://www.sicb.org/meetings/2014/). Feel free to contact the organizers if you have any questions.

Organizers:

Deirdre Lyons, Postdoctoral Researcher, Duke University (deirdre.lyons@duke.edu)

Mansi Srivastava, Postdoctoral Fellow, Whitehead Institute (mansi@wi.mit.edu)

Mark Martindale, Directory, Whitney Marine Laboratory (mqmartin@whitney.ufl.edu)

Funding Opportunities:

Some funding is available for those who present a poster or talk as part of this symposium to help defray the cost of attending the meeting. Preference will be given on a primarily need basis to junior scientists (students, post-docs and junior faculty), current members of the Society for Developmental Biology (SDB), and those from under-represented minorities and those with disabilities.  To apply, send an email by September 1, 2013 to Dede Lyons (deirdre.lyons@duke.edu) with the following information:

1) Name, institution, lab and position (student, post-doc, etc.)

2) The title and abstract of your poster or talk. Please indicate if you requested a talk or poster

3) Indicate whether you are a current SDB member and/or belong to an under-represented minority or have a disability

3) Cost of attending the meeting, broken down by travel, lodging, and registration costs

4) Alternative funding sources and amounts available to you

5) The amount you are requesting for funding from the symposium

Other sources of funding are available through SICB:

http://www.sicb.org/students/awards.php3#support

http://www.sicb.org/students/skinner.php3

Confirmed Speakers:

Sally Horne-Badovinac 

Assistant Professor, Molecular Genetics and Cell Biology University of Chicago)

(http://shb-lab.org/)

Title: “Mechanisms of egg chamber elongation in Drosophila”

Ed Munro 

Professor, Molecular Genetics and Cell Biology University of Chicago

(http://munrolab.bsd.uchicago.edu/index.html)

Title: “Dynamics of tissue morphogenesis in ascidians”

Jennifer Zallen 

SICB_CellEvoDevoAssociate Member, Sloan-Kettering Institute

(http://www.mskcc.org/research/lab/jennifer-zallen)

Title: “Co-ordination of cell movements to shape tissue morphology in Drosophila”

Dave McClay 

Professor, Department of Biology Duke University

(http://fds.duke.edu/db/aas/Biology/david.mcclay)

Title: “Sequential control of morphogenesis and pattern formation in the sea urchin embryo”

Bob Goldstein 

Professor, Biology Department UNC Chapel Hill

(http://labs.bio.unc.edu/Goldstein/index.html)

Title: “Using C. elegans and other organisms to understand conserved mechanisms of morphogenesis”

Matt Gibson 

Associate Investigator, Stowers Institute for Medical Research

Assistant Professor, Anatomy and Cell Biology University of Kansas School of Medicine

(http://research.stowers.org/gibsonlab/)

Title: “Cellular and molecular mechanisms of tentacle morphogenesis in the sea anemone Nematostella vectensis”

Reiko Kuroda 

Professor, Department of Life Science University of Tokyo

(http://bio.c.u-tokyo.ac.jp/labs/kuroda/englishpage.htm)

Title: “How a single gene twists a snail”

Leslie Babonis 

Postdoctoral Researcher, Kewalo Marine Laboratory

(http://www.kewalo.hawaii.edu/martindale/mmpeople.html)

Title: “The influence of the extracellular matrix on differentiation of cnidocytes”

Josien van Wolfswinkel 

Postdoctoral Associate, Whitehead Institute for Biomedical Research

(http://jura.wi.mit.edu/reddien/)

Title: “Heterogeneity in planarian neoblasts by single cell analysis”

Alexa Bely 

Associate Professor, Department of Biology, University of Maryland

(http://www.life.umd.edu/biology/bely/web/belylab/home.html)

Title: “Using live imaging to probe the cellular basis of annelid regeneration”

John Wallingford 

Associate Professor, Molecular Cell and Developmental Biology University of Texas Austin

(http://www.bio.utexas.edu/faculty/wallingford/)

Title: TBD

Supported by:

SICB Divisions: DEDB, DIZ, DNB, DPCB, DVM

American Microscopical Society

Society for Developmental Biology

(1 votes)

Loading...

This interview first appeared in Development.

François Guillemot heads the Division of Molecular Neurobiology at the MRC National Institute of Medical Research (NIMR) in London. His research focuses on the transcriptional control of neurogenesis, adult neurogenesis and the epigenetic regulation of gene expression in neural development. François recently became an editor for Development, and we asked him about his research and career, as well as his lab’s future move to the Crick Institute.

When did you first become interested in developmental biology?

I have always been interested in biology, but my first interest was zoology. I spent a lot of time on the French coast, in Brittany, observing little animals at low tide. That was really a great passion of mine when I was young. As developmental biology is closely linked to zoology, the move was quite logical.

What projects are your lab working on at the moment?

My lab’s research focuses on neural stem cells and how their fate is regulated at the molecular level. We have two main current directions. One of these is to examine the gene regulatory networks that control neural stem cell decisions: to self-renew, to differentiate into one cell type or another, or to remain quiescent. This work is mostly performed in neural stem cell cultures. Our other focus is on understanding the function of individual genes in neural stem cell fate decisions in vivo, either in the developing or the adult brain.

There has been some controversy as to whether the mouse brain is a good model for the human brain. Do you think it is a good model for the particular questions that you are asking?

The mouse is obviously the closest animal model to humans and the easiest one to work with. It is a good system by default. But it is far from being a perfect model, particularly for the development of the cerebral cortex. Great work has been done looking at the cellular organisation of the human foetal cortex, and there are very striking differences to the mouse. But for other aspects, such as adult neurogenesis, I can’t really answer the question of how close the mouse is to the human because there is still so little known about neurogenesis in the adult human brain. I think that an important future direction of research in the field is to better understand the human brain and to develop tools to achieve this, such as in vitro systems that can be used to probe human brain development. Some great progress is being made in that direction at the moment.

You started your career working on the development of the immune system and then moved to developmental neurobiology. Why did you change fields, and what kind of parallels are there between the immune system and the nervous system?

I think I am far from being the only one who changed from an early career in the immune field to neuroscience. My feeling at the end of my PhD was that many of the key discoveries in the immunology field had been made, and what remained to be done was to acquire a deeper understanding of the details, rather than the big picture. At the time, being young and naïve, I wanted to address the big questions that remained unanswered. The neuroscience field seemed to be the most appropriate for this kind of research.

The transition was not that difficult because immunology and neuroscience have in common the fact that the two systems encompass substantial diversity in cell types and cellular responses. You become used to dealing with very complex systems, and in trying to understand where this diversity comes from. However, in practice most of the things that I learned in my PhD and applied later on are maybe more technical. My knowledge of molecular biology (although maybe a bit outdated now!) comes from my PhD work, and I applied that molecular approach to my work in neurodevelopment.

You did your undergraduate and postgraduate studies in France, then you moved to the USA and Canada, and then you came back to Europe. How does the research environment differ between France, North America and the UK?

It is obviously very different and I always try to avoid grading the different systems because every system has its advantages and disadvantages. I think that the British system, where I am now, is very well balanced. I really enjoy the flexibility that it has, giving you the ability to adapt and move on in terms of topics and techniques, probably more than in France. In the UK there is a greater turnover of PhD students and postdocs in the lab than in France, where a larger fraction of the lab is usually considered permanent staff. This stability is great in that it provides continuity, but it is harder to renew, to find new approaches, questions, or to decide to change direction – you need to convince not just yourself and the new people you recruit, but also everyone you are working with already. The British system also provides a good balance between competitiveness and still being collaborative and convivial.

Was it useful for you to move countries?

Certainly, both intellectually and personally. Moving allows you to take a step back and make what you think at the time is the right decision. You are not influenced by earlier decisions that you are obliged to follow because you remain in the same system. By moving countries you start anew, and you can really decide what the question is that you really want to address. Whenever I have the opportunity to recommend something to a young scientist, I encourage them to take full advantage of the great opportunity that scientists have to be able to move around to do research in the best conditions.

Did you have a mentor or someone who inspired you or gave you good advice during your early career?

Not a single person. I have taken advice by asking specific questions of the people around me. But Nicole Le Douarin, who was my first thesis supervisor, was a great figure. She was very inspiring, of brilliant intellect and with a real understanding of her system. It made me realise that understanding your experimental model in depth is a great strength, as well as asking the right questions and addressing them with the right techniques. But in terms of career advice, I am more of an improviser: I ask around and then follow my opinion.

How did you find your first months as a Development editor?

I was looking forward to it. It was very attractive to work with a great group of colleagues and for a journal that I respect a lot. But I was a little apprehensive of the amount of work, and how much of a distraction it would be to my main occupation. But I have really enjoyed it actually. The volume is manageable and it is different from the daily lab work, so I can easily do it at different times and almost as a diversion from mainstream work. It is quite diverse, and the interactions with authors through their research is something that I enjoy a lot. To see a manuscript, which has real potential but clearly can be improved, to read the diversity of opinions of reviewers and to see the improvements through the revisions: I find this process interesting and most of the time it ends very positively. Another concern I had was how often you have to deal with complicated situations in which people really disagree and you have to arbitrate, but fortunately I haven’t encountered this kind of situation yet.

Are there any particular papers that you would like to see submitted to Development?

I am fully behind the current effort by the Development team to increase the visibility of the journal in the stem cell field. My work is partly brain development, partly stem cells, so I am aware of the need for Development to raise its profile further in the stem cell field, so that it becomes as recognised and important in this area as it is in neural development. Another obvious direction in the mid to long-term is to move more towards the human as a model of development. Papers that describe human development, such as those using in vitro models of organ development, would be very welcome.

Your lab will be moving to the new Crick Institute in the near future. What are your expectations?

My understanding of the vision of the director, Paul Nurse, of how an institute should be run is that you should hire the best scientists and let them decide what they want to work on. I am very happy with this way of thinking. What I am really looking forward to is to have new colleagues. The Crick Institute is a merger of our institute (NIMR) with Cancer Research UK institutes in London together with contributions from three London universities. That will greatly increase the number, but also the diversity, of research that is being done. I look forward to having more contact with cell biology and disease model groups. The NIMR is currently a very interactive place, so it is both our wish and our challenge to make the Crick Institute, which will be at least twice as big, as collaborative as the NIMR is at the moment.

What advice would you give to young researchers?

I think the best research is done by people who get ideas that other people don’t get. So, follow your intuitions and desires, and don’t follow advice if it goes against these. And don’t hesitate to move, both geographically and in topic, between your PhD and postdoc. Basically, don’t be too conservative.

What would people be surprised to find out about you?

Unfortunately, I am not great at cooking which, given that I am French, can sometimes take people by surprise. I love nature and wildlife, and when I moved to the UK I discovered gardening. I have taken my own approach to gardening, and I mostly take care of the weeds that happen to land in my garden. I use my garden as a way to get closer to nature and watch animal behaviour and plant growth – a place for daily observations of wildlife. I enjoy it a lot and it is my way to relax.

(4 votes)

Loading...