Blog entry

When thinking Barcelona, what first comes to mind is probably the football and Olympic games, the beaches, relaxed Mediterranean lifestyle, siesta and long nights out. All of it is accompanied with the Gaudi’s whimsical architecture at the background as an extra bonus. People usually go to Barcelona for a vacation or … for a science meeting. I was in this colorful city already several times because of science and always loved the place. And then a perfect chance came to spend a little bit more time in Barcelona when I was awarded the Development Travelling Fellowship supporting my visit for collaborative purposes. I was hosted by the lab of Enrique Martin-Blanco at IBMB at the University of Barcelona and the main goal of my stay was to work out the conditions for measuring protein activity during early zebrafish development. I embraced this opportunity to learn more about the place and its local customs by living there. What follows, are some of the experiences I have made in those two months in Barcelona.

Science reflection

Despite the economical situation and the ever-tightening budget, people do amazing science in Barcelona. I was exposed to a rich spectrum of different projects during the lab group meetings and also during department seminars. The microscopy facilities were impressive and I was happy to have more that one choice for a particular setup to use in my experiments. I could test different excitation and emission combinations as well as various optical variants to find the best conditions for imaging. Although the facilities were very busy and shared by many labs, I could get access to all the necessary equipment to conduct experiments and collect enough data that kept me busy with the analysis when the microscopes were occupied by other data hunters. Here, I would like to express my deep gratitude to the members of Enruque’s lab and to the heads of the facilities for making my time there very smooth in terms of organization and planning. The first two weeks were made very easy for me, because the girls who were working with zebrafish, made all the necessary arrangements such as booking injection stations and the microscope slots, preparing certain reagents and also making spare time to show me around. This was an enormous help during the short visit when every second counts.

As other travelers here had already commented, a good thing about going to a different place is that it allows refreshing ones thinking and the general attitude to the lab routines. For example, it became clear very quickly how spoiled we are back home in Germany. While it is good to focus on the work without thinking much about the costs involved, one can get easily carried away and waste unduly amount of reagents and materials. While I never felt limited in any reagent or equipment I had to use during my visit, it became apparent how important is to be economical in the way one works. For example, it is perfectly possible reusing the plastic Petri dishes in which the embryos are kept, which is often for half a day only. There is no good reason for discarding the dishes. It is not about the cost of the dishes, which is rather low, bur more about the plastic waste that is generated that way. Certainly, it made me think more carefully of the amount of waste produced in a lab and I keep applying my new working habits.

Cultural differences

When in Spain, do like Spanish do, or at least try to. I was very curious about the local customs and the differences between the Spain and Germany.

People in Barcelona are very friendly and one can easily get around with speaking English, but knowing a few words in a local language would definitely be helpful. Barcelona is the capital of Catalonia, therefore there are two official languages spoken in Barcelona: the Catalan and Castilian Spanish, which could be very confusing at the beginning, especially when trying to read the signs. It always makes a nice impression if you could say “bom dia” instead of “bueans dias” and some other simple phrases in Catalan.

Strangers at the street and in a public transport stare at one another much more directly than they do in Germany. That was a striking difference from the way the strangers interact in Northern Europe, where people mind their own businesses. The personal distance is much shorter and in the metro it would be very normal to lean over to see better the book a fellow passenger is reading.

For someone who is used to have a lunch break at 11:30, which is typical in Germany, it might be a bit unusual to shift this time for an hour or more. People in Spain normally go for lunch around 1 pm or later. It is very typical to conclude the lunch with a coffee and maybe a cigarette.

It was relatively easy to find a place to stay. I got a room in a shared apartment with four other people in a very nice neighborhood with large streets and beautifully designed houses. Every day going to the metro, I would fight my way to get in because of the tourists crowding in front of casa Battlo, one of the famous Gaudy houses turned into museum, right next to the station. My flatmates were on various kinds of the study exchange programs or other types of visits and all from different backgrounds, which was a very enriching experience. I feel very lucky with my choice because I had the nicest flatmates, easygoing and very friendly.

Although it is acceptable, I would not advice drinking the tab water. It is full of chlorine, which gives a peculiar taste to it. The bottled water is relatively cheap and the 5 to 8 liter cans are available everywhere. Barcelona is rather expensive city but good deals are possible. There are plenty of grocery stores and little private kiosks that run till late but the price range could be huge and I spent some time comparing prices before deciding where to shop.

The sunlight is very intense in Barcelona and I was constantly using sunglasses. My room had no curtain and the effect was amazing: I did not need an alarm clock anymore getting up with the sun every day. If only the sun could get up a bit later on the weekends!

Barcelona is generally a very safe city but one must be wary of the theft, which is apparently a very popular business in the tourist areas. It is well known and has been discussed thoroughly in many blogs giving travel advices. The thieves will try to steal the stuff from you while you are admiring the architecture and other street wonders. Being vigilant and keeping an eye on your belonging is enough to stay away form the trouble.

How to find a piano

While this would not be an issue for the most visiting scientists, I felt desperate facing with the idea of spending two months without a piano. That’s why during the first week I kept annoying my colleagues asking them to call different piano stores and enquire about a possibility of renting one. Soon it became clear that renting a piano for two months is not an option. I found a place nearby where I could play for a small fee, but I could never make it there during the opening hours. At the end I was quite lucky to find a cheap digital piano on ebay, which I could later re-sell to one of the colleagues who got inspired and decided she wanted to perfect her musical skills.

(3 votes)

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A group of graduate students at MIT have written a letter on behalf of American graduate students, urging the United States Congress not to cut science funding. The Congress Joint Select ‘super’ Committee on Deficit Reduction will make their decision later this week, and today is the last day to sign the letter.

If you’re in the US, have a look at the Stand With Science website for more info.

(1 votes)

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Applications are invited for a post-doctoral research scientist post in Melbourne, to join a newly funded research group within the Cancer Cell Biology Program. The research focuses on understanding the mechanisms regulating the growth of neural stem cell derived tumours in Drosophila. We are part of a vibrant fly community working alongside 400 cancer biologists located in the centre of Melbourne.

Funding is available for 3 years, starting July 2012. Candidates should have a PhD in developmental biology or cell biology, proven experience in molecular biology, immunohistochemistry and/or biochemistry, experience in fly genetics is also desired. For more information and application, please write to Dr Louise Cheng at lcheng@nimr.mrc.ac.uk

References:

1. Cheng et al. Anaplastic Lymphoma Kinase Spares Organ Growth during Nutrient Restriction in Drosophila. Cell (2011) vol. 146 (3) pp. 435-47

2. Sousa-Nunes et al. Regulating neural proliferation in the Drosophila CNS. Curr Opin Neurobiol (2010) vol. 20 (1) pp. 50-7

3. Maurange et al. Temporal transcription factors and their targets schedule the end of neural proliferation in Drosophila. Cell (2008) vol. 133 (5) pp. 891-902

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The web comic Piled Higher and Deeper (PHD) has been commiserating with graduate students since 1997. And now you can watch the comics come to live on the big screen, as universities and institutes across the world (including Antarctica!) are screening the PHD movie.

Fans of the comic will recognize most of the jokes, but now the individual 3-panel strips have been turned into a full-length movie with a plot that summarizes the main story of the long-running comic. The film was shot in its entirety at the Caltech campus last spring, and all actors are students and staff from Caltech. As they’re by and large professional scientists rather than professional actors, the acting isn’t always very sharp, but they did a great job at bringing the comics to life. The trailer below gives a good indication of the film.

PHD Movie Trailer from PHD Comics on Vimeo.

Most screenings are only open to students from the hosting institution, but I was lucky to hear about an open screening at University College London. Even though the screening was open to absolutely everyone, the lecture theatre was not entirely full. Perhaps it really does appeal specifically to grad students? Nevertheless, the people who did attend seemed to enjoy the film, and laughed at every joke. Even the ones that you could see coming from a mile away if you were familiar with the comics.

But this was not just any screening: it was one of the few that PHD Comics creator Jorge Cham was attending. After the film, science-loving comedian Robin Ince hosted a Q&A with Jorge and with Alex Lockwood – the actress (and graduate student!) who plays the character of Cecilia in the film. Alex initially kept her role in the film a secret from her advisor. “I didn’t tell him I was doing it for a while, but his wife is really nosy on Facebook…” Once he found out, he was a lot more excited about the film than she was – as long as she still got her work done, of course.

Despite being based largely on the existing comic strips, the end of the film breaks a longstanding tradition. In the fourteen years that Piled Higher and Deeper has been running, the main character was never named. In the film, he finally introduces himself. When this came up during the Q&A, Jorge explained why the student didn’t have a name to begin with: “First I was just kind of lazy, but then it became a funny thing. It took my own professor about four years until he learned my name.” But now, wanting to give the film a more interesting resolution, the student gets a name. “I figured it was about time. And I can always deny that it’s not comic-canon, that it’s just movie-canon…”

After the Q&A, we caught up with Jorge and asked him how the film translates to international audiences. It’s set in the US, where PhD degrees can regularly take 5-7 years, and many jokes are based on the fact that graduate school takes forever. My own favourite joke involves Cecilia’s encounter with a high school classmate:

But in the UK, where several universities have now screened the film, PhD degrees are much shorter than in North America. Do the jokes hold up?

“Well I heard that the guitarist from Queen took 35 years to finish his PhD, so I think he pulls up the average,” jokes Jorge, “But I think what translates the most is that feeling of uncertainty, feeling stuck and not being quite sure what you’re going to do next. That’s international.”

Regular readers of the Node may recall that we’ve interviewed Jorge before, and that he mentioned a “biologist character” that would appear in the comic very soon. What is happening with that, we wanted to know. “That’s still coming, but probably not for another year, at least.” Aww. But of course, this is the man who has turned procrastination into a career: Jorge left research several years ago to pursue the comic full time, and to give talks about procrastination to graduate students. To tie in with the various posts we’ve had on the Node about alternative careers, we asked him what he learned in his PhD degree that he still uses today.

“Many things. I think part of what I do as an artist is trying to discover where the truth is – or at least ask the question “where is the truth?” – and being able to think analytically in a big picture sense but also being able to drill down, and work on the minutiae of the details. I think the PhD gives you that kind of macro/micro vision at the same time. But mostly it just gives me the ability to avoid questions…”

If you’d like to see the movie yourself, here is a list of places that are showing it. And if you’re a bit more patient (now there’s something you learn in grad school!) you can wait for the DVD release, tentatively planned for Pi Day (March 14) next year.

(6 votes)

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A new Nature study has again demonstrated the power of ES cells as a model system for recapitulating developmental processes in vitro. Following on from the amazing self-assembly of differentiated optic-cups reported earlier this year, Yoshiki Sasai’s latest work has resulted in the generation of functional pituitary gland tissue from mouse ES cells.

Using a modification of their 3D floating aggregate culture protocol (which can generate complex patterned neural structures), Sasai’s group, from RIKEN CDB in Kobe, Japan, observed the generation of small ectodermal pouches, which expressed markers typical of adenohypophysis (anterior pituitary) maturation.

During embryogenesis, adenohypophysis development is dependent on the interaction of two distinct neural tissues: Pitx1-positive rostral head ectoderm, and Rx-positive rostral hypothalamic neuroectoderm. By using greater cell numbers to establish ES-cell aggregates than in their previous reports, both of these tissue types were generated together. Pitx1-positive ectoderm formed an outer layer, with sheets of Rx-positive tissues within. Regions of Pitx1-positive ectoderm were then observed to express the adenohypophysis marker Lim3, invaginate, and bud, forming vesicles in a manner consistent with normal pituitary development.

Reprinted by permission from Macmillan Publishers Ltd: Nature doi:10.1038/nature10637, copyright (2011)

Reference:
Suga, H., Kadoshima, T., Minaguchi, M., Ohgushi, M., Soen, M., Nakano, T., Takata, N., Wataya, T., Muguruma, K., Miyoshi, H., Yonemura, S., Oiso, Y., & Sasai, Y. (2011). Self-formation of functional adenohypophysis in three-dimensional culture Nature, 480 (7375), 57-62 DOI: 10.1038/nature10637

(4 votes)

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Research Associate

University of Cambridge – Cambridge Institute for Medical Research, Department of Haematology

Salary: £27,428 – £35,788 pa

The funds for this post are available until 30 April 2014 in the first instance.

Applications are invited for the post of a postdoctoral Research Associate in the group of Dr. Katrin Ottersbach. Research in this group focuses on the developmental origins of haematopoietic stem cells and the molecular mechanisms regulating their generation, with a particular emphasis on how these processes are relevant to understanding blood malignancies.

The work will involve a number of molecular biology techniques, including miRNA profiling, deep sequencing, knockdown and overexpression studies, histological analysis and general cell biology techniques. Experience in any of these techniques and a background in haematopoiesis, developmental biology, leukaemia and/or miRNA biology would be of a particular advantage.

Formal applications, including CV, plus a completed CHRIS/6 form, parts I and III (available at: http://www.admin.cam.ac.uk/offices/hr/forms/chris6/) should be sent to: Ms Helen Milton, Department of Haematology, Cambridge Institute for Medical Research, Hills Road, Cambridge CB2 0XY, e-mail: hem28@cam.ac.uk

Quote Reference: SB09172

Closing Date: 2 December 2011

Interview Date(s): 14 and 15 December 2011

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California State University Monterey Bay
Tenure Track- Full Time

Starting Date Fall 2012

The Department of Biology in the Division of Science and Environmental Policy, California State University Monterey Bay invites applicants for a tenure track Assistant Professor of Evolutionary Developmental Biology.  Candidates should have a PhD in Biology or related field at time of hire, demonstrated excellence in biology instruction, expertise in developmental biology and excellent written and oral communication skills.  The successful applicant will teach upper-division developmental biology courses and teach other courses that may include evolutionary biology and population genetics, and assist with teaching of the introductory biology series for majors.  They will develop and maintain a research program that includes undergraduates; and contribute to the curriculum development and other service to the university.  CSUMB is located on California’s Central Coast and serves a diverse cultural, ethnic, and economic population.  Letters of recommendation should not be forwarded until requested.  Further details about the position and how to apply may be found here: https://mocha.csumb.edu/uhr/jobs/job_announce.jsp?job_number=FAC2011-169&req_id=001408 Interested candidates are welcome and urged to contact Dr. Steve Moore (stmoore[at]csumb.edu) for detailed information about CSUMB, SEP, the Biology program or the specific demands of this position.
Open until filled.  Application Screening Begins: January 9, 2012

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Next time you curse your hair for your bad hair day, consider thanking it instead.  The hair follicle has populations of stem cells that aid in skin regeneration after injury, and a recent Development paper unravels a new role for the transcription factor Lhx2 in this process.

Populations of epithelial stem cells in hair follicles serve to rebuild the hair bulb during the normal hair cycle throughout our lives, but they also can migrate to wounded skin in order to aid in skin regeneration.   This ability is quite handy—when the skin in a hairy area is injured, it heals faster and more efficiently than a wound on skin without hair.  Recently, a research group illuminated the importance of the transcription factor Lhx2 in the repair of injured skin by hair follicle stem cells.  Lhx2 functions in organ development, cell fate determination, and stem cell activity in some organs.  In hair follicles, Lhx2 was previously known to regulate the switch between stem cell maintenance and activity.  In their recent report, Mardaryev and colleagues found that Lhx2+ hair follicle cells co-express several stem cell markers.  Following injury, proliferating cells in the adjacent hair follicle were positive for Lhx2 expression, as seen in the images above.  Lhx2 (magenta) expression increases by days 3 and 5 following injury.  Most of the dividing cells (green) also are Lhx2+.  In addition, cell proliferation following injury was reduced in heterozygous Lhx2 knockout (+/–) mice.   Lhx2 ensures wound re-epithelization through its regulation of Sox9 and Tcf4, while at the same time inhibiting normal hair follicle cycling via Lgr5 regulation.

For a more general description of this image, see my imaging blog within EuroStemCell, the European stem cell portal.

 
Mardaryev, A., Meier, N., Poterlowicz, K., Sharov, A., Sharova, T., Ahmed, M., Rapisarda, V., Lewis, C., Fessing, M., Ruenger, T., Bhawan, J., Werner, S., Paus, R., & Botchkarev, V. (2011). Lhx2 differentially regulates Sox9, Tcf4 and Lgr5 in hair follicle stem cells to promote epidermal regeneration after injury Development, 138 (22), 4843-4852 DOI: 10.1242/dev.070284

(2 votes)

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Here are the highlights from the current issue of Development:

Skin-deep dermal niches

Hair follicle formation in the epidermis depends on signals from the underlying dermis and normally only occurs during late embryonic and early neonatal life. However, epidermal activation of β-catenin can induce follicle formation in adult mouse skin. One possible explanation for this observation is that epidermal cues can reprogram adult dermis to a neonatal state. On p. 5189, Fiona Watt and co-workers investigate this possibility by examining dermal fibroblasts from adult and neonatal mice. The researchers show that the gene expression profile of adult dermal fibroblasts isolated from skin in which β-catenin has induced ectopic follicles resembles that of neonatal fibroblasts rather than that of fibroblasts isolated from uninduced adult skin. This dermal reprogramming seems to originate within a specific subpopulation of fibroblasts near the hair follicle junctional zone and results in fibroblast proliferation and extracellular matrix remodelling. Together, these results suggest that the adult dermis is an unexpectedly plastic tissue, and that epidermal stem cells and their dermal niche exist in a state of dynamic interdependence.

Self-duplicating escorts for germ cells

During Drosophila egg development, differentiated germ cells, which are produced by germline stem cells (GSCs), are accompanied by escort cells (ECs) to the centre of the germarium, where the germ cells form egg chambers. It has been proposed that these ECs are generated by a population of escort stem cells, but Ting Xie and co-workers now overturn this idea (p. 5087). The researchers show that ECs undergo slow turnover and that lost cells are replaced by self-duplication rather than by stem cell division. Using fluorescent markers, they show that ECs extend elaborate cellular processes that interact with differentiated germ cells and that these processes are missing when GSC differentiation is blocked. Conversely, disruption of Rho function in ECs, which disrupts the formation of EC processes, leads to the accumulation of ill-differentiated single germ cells and the gradual loss of ECs. These findings reveal a mutual dependence between ECs and differentiated GSC progeny, and suggest that self-maintained ECs form a niche that controls GSC lineage differentiation.

Lens invagination Shrooms along

Epithelial invagination, a common feature of embryogenesis, involves coordinated modulation of individual cell cytoskeletons. For example, during eye development, lens pit invagination, which is accompanied by a columnar-to-conical cell shape change (termed apical constriction, AC), is dependent on the cytoskeletal protein Shroom3. Now, through experiments in chick and mouse embryos and in MDCK cells, Richard Lang and colleagues provide new insights into how Shroom3 drives AC and lens invagination (see p. 5177). The researchers show that the activity of Rock1/2 (serine/threonine kinases that activate non-muscle myosin and that are activated by the Rho family GTPase RhoA) is required for lens invagination and that RhoA activity is required for Shroom3-induced AC. RhoA, when activated and targeted apically, is sufficient to induce AC, they report, and is essential for the apical localisation of Shroom3. Finally, they show that the RhoA guanine nucleotide exchange factor Trio is required for Shroom3-dependent AC. Thus, a Trio-RhoA-Shroom3 pathway is required for AC during lens pit invagination.

Merlin casts a spell over glial cell proliferation

Glial cells perform many essential roles in the nervous system but how are their numbers controlled during development? Here (p. 5201), Venugopala Reddy and Kenneth Irvine report that glial cell proliferation in Drosophila is regulated by Hippo signalling, a conserved signalling pathway that controls organ growth and size. They show that Yorkie, the transcriptional co-activator of Hippo, is necessary for normal glial cell numbers and drives glial cell overproliferation when overexpressed. Yorkie activity in glial cells, they report, is controlled by a Merlin-Hippo signalling pathway; other upstream regulators of Hippo (for example, Fat) play no detectable role in glial cell proliferation. They also show that Yorkie affects glial cell proliferation by promoting the expression of the microRNA gene bantam, which, in turn, promotes Myc expression. Because homologues of Merlin, Yorkie and Myc are implicated in human glioma development, the authors suggest that the regulatory links identified here could represent a conserved pathway for the control of glial cell proliferation.

String-ing out stem cell homeostasis and aging

Stem cells contribute to tissue homeostasis throughout life by producing differentiating daughter cells. Consequently, a decline in stem cell proliferation is thought to be involved in tissue aging. But what regulates the cell cycle in stem cells? On p. 5079, Yukiko Yamashita and colleagues report that String (Stg), a homologue of the cell-cycle regulator Cdc25, controls stem cell maintenance, proliferation and aging in Drosophila testes. The researchers show that Stg is highly expressed in germline stem cells (GSCs) and in cyst stem cells (CySCs), the two stem cell types present in Drosophila testes, and that Stg is required for GSC and CySC maintenance and proliferation. Moreover, Stg expression declines with age in GSCs, and this decline is a major determinant of the age-related decline in GSC and CySC function. Notably, restoration of Stg activity reverses this age-associated phenotype but also leads to late-onset tumours. The researchers propose, therefore, that Stg/Cdc25 is a crucial regulator of stem cell function during tissue homeostasis and aging.

Brainy new role for Pax6

Successful development of the brain requires the tight regulation of sequential symmetric and asymmetric cell division. The molecular machinery that regulates the mode of cell division during mammalian brain development is poorly understood but now Magdalena Götz and colleagues show that the transcription factor Pax6, a known regulator of neurogenesis and proliferation, regulates both the orientation and mode of cell division in the mouse cerebral cortex (p. 5067). Using live imaging, the researchers show that, in the absence of Pax6, there is an increase in non-vertical cellular cleavage planes in the cerebral cortex. This phenotype, they report, seems to be mediated by the Pax6 target Spag5, which is a microtubule-associated protein. Moreover, long-term live imaging in vitro shows that Pax6-deficient progenitors generate daughter cells with asymmetric fates at higher frequencies than wild-type progenitors. From these and other data, the researchers propose that Pax6 plays a cell-autonomous role in the regulation of cortical progenitor cell division that is independent of apicobasal polarity and cell-cell interactions.

Plus…

Chromosome silencing mechanisms in X-chromosome inactivation: unknown unknowns

In this issue, fifty years after Mary Lyon proposed her X-chromosome inactivation (XCI) hypothesis, Neil Brockdorff discusses the molecular mechanisms of chromosome silencing during XCI, focusing on topics in which new findings are challenging the prevailing view. See the Review Article on p. 5057

Fifty years of X-inactivation research

The third X-inactivation meeting ‘Fifty years of X-inactivation research’, which celebrated the fiftieth anniversary of Mary Lyon’s formulation of the X-inactivation hypothesis, was an EMBO workshop held in Oxford, UK, in July 2011. Gendrel and Heard review the results presented at the meeting and highlight some of the exciting progress that has been made in this field. See the Meeting Review on p. 5049

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Dates for your calendar
This is a selection of upcoming dates of interest, but it’s by no means an exhaustive list. We’ll try to do these once in a while, but don’t hesitate to write your own posts to let people know about similar deadlines, or leave a comment below. Also make sure to check the eligibility of all scholarships and grants before applying.

Conference registration opening.
November 8 – Start of abstract submission for the ISSCR meeting (June 13-16, 2012)
December 1 – Start of registration for the ISSCR meeting

Conference registration deadlines.
Keystone announced a few upcoming deadlines for conference abstract submissions, including dates for the following meetings:
November 9 – abstract & scholarship deadline for “The Life of a Stem Cell: From Birth to Death” (March 11-16, 2012)
November 16 – early registration deadline for “Angiogenesis: Advances in Basic Science and Therapeutic Applications” (January 16-21, 2012)
November 17 – early registration deadline for “Epigenomics” joint with “Chromatin Dynamics” (January 17-22, 2012)
November 22 – early registration deadline for “Cardiovascular Development and Regeneration” (January 22-27, 2012)
November 30 – abstract & scholarship deadline for “Non-Coding RNAs” joint with “Eukaryotic Transcription” (March 31 – April 5, 2012)

Grants and fellowships:
November 18 – Application deadline for the NSF Graduate Research Fellowship Program (GRFP)
December 16 – Application deadline for the Wellcome Trust’s New Investigator Award
December 16 – Application deadline for the Wellcome Trust’s Senior Investigator Award

Travel funding:
December 1 – The very last day to apply to The Company of Biologists Direct Travel grants, which fund travel for conference attendance. These grants are being discontinued.

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