Recruiting 16 motivated students from around the world to join a fully-funded four year PhD programme in an international scientific environment at the Novo Nordisk Foundation Research Centers. Positions starting September 2021. Applicants of all nationalities may be awarded funding, provided they fulfill all of the eligibility criteria.
Programme Outline
The four-year programme is divided into a pre-doctoral year followed by three years of PhD training at one of the four Novo Nordisk Foundation Research Centers based at the University of Copenhagen or the Technical University of Denmark:
The pre-doctoral year includes short rotation projects, choice of a lab for the long-term (PhD) project, and common research-based courses. Approximately 15% of time during the pre-doctoral year is spent on courses, and the rest of the time on research. Awardees must pass an assessment at the end of the pre-doctoral year to qualify for the following three years of PhD education.
Supervisors and Research Areas
Applicants pre-select one of the four Novo Nordisk Foundation Research Centers in their application. Each Center conducts research in several connected research areas in biotechnology or biomedicine. CBMR investigates how the interaction between genes and environment affects human metabolism, CFB promotes a sustainable biobased chemical industry using specifically designed cell cultures (cell factories) to produce chemicals and pharmaceuticals, CPR works on integrative protein technologies, and DanStem investigates stem cell differentiation and the role of cancer stem cells in different types of cancer. See the programme website, application webpage, and Center websites (links above) for more information.
Potential supervisors and projects are listed on the programme website: Potential Supervisors
The research project will consist of studying how cells become different from one another, forming spatial patterns of different cell types in plant tissues such as the leaf epidermis and the shoot meristem. This will involve time-lapse microscopy, quantitative image analysis and mathematical modelling. This position is initially for 3 years and can start from January 2021, although the start date is flexible.
We are seeking a highly motivated candidate that is willing to combine computational and experimental work in plants. The ideal candidate would have a PhD in Quantitative Biology, Systems Biology, Biophysics or a related field. Applicants coming from Physics, Maths, Computer Science, Engineering background or related fields are also very welcome to apply. The applicant should have expertise in, at least, one of the following topics: quantitative image analysis, quantitative time-lapse microscopy and/or mathematical modelling. Some experience in programming is expected.
Application Deadline: November 18th 2020.
See the full advert and application instructions in the following link .
Meyer HM, Teles J, Formosa-Jordan P et al. (2017) Fluctuations of the transcription factor ATML1 generate the pattern of giant cells in the Arabidopsis sepal. Elife. 6, 1–41.
Formosa-Jordan P, Teles J and Jönsson H (2018) Single-cell approaches for understanding morphogenesis using Computational Morphodynamics, in Mathematical Modelling in Plant Biology, Morris R (eds) (Springer, Cham).
Torii KU (2012) Two-dimensional spatial patterning in developmental systems. Trends Cell Biol 22(8): 438–446.
The wings of vertebrates, like birds and bats, emerged relatively recently, and we understand that these wings evolved from forelimbs. Even for the mythological dragon there seems to be a consensus (at least in recent depictions) that their wings are also derived from their forelimbs. Insects, however, possess both wings AND limbs on their winged segments, suggesting that their wings are not evolved from modified limbs, which begs the question “where did insect wings come from?” Despite their status as the first animals to take to the skies, the answer to this question has remained poorly understood and under debate for over 200 years1,2. This debate has culminated in two leading hypotheses on the origin of insect wings, each linked to different origin tissues: a lateral outgrowth of the dorsal body wall (tergum) and ancestral proximal leg structures (pleuron in insects)2.
Historically, scientists have attempted to dissect the evolutionary origin of insect wings through identifying structures related to wings in non-winged segments of insects (wing serial homologs) and other wingless arthropods (wing homologs)3. The idea behind this approach is that the wing homologs in other segments have been modified to differing degrees, suggesting that wing homologs from wingless segments might provide us with a series of “snapshot” views into the evolution of wings and help us reconstruct how this complex structure came to be. Until relatively recently, attempts to identify wing-related structures in non-winged segments relied on these structures sharing morphological similarity with wings (i.e. looking like wings), which understandably limited the identification of wing homologs. Recently, with the application of molecular evolutionary and developmental biology (evo-devo) approaches, the diversity of the tissues identified as wing homologs has increased3. Some of these studies have even provided evidence that insect wings are not derived from either tergum or pleuron (ancestral proximal leg), but potentially from a combination of these two tissues (i.e. they have a dual origin)4–9.
In our recent paper, we applied this molecular evo-devo approach to the identification of wing-related structures in a crustacean10. The reasoning behind looking for “wings” in a crustacean is that crustaceans and insects share a common ancestor. Therefore, by identifying the potential wing homologs of a crustacean and comparing them to the wing serial homologs of insects, we can gain a better understanding of what tissues were present in the common ancestor of these groups that had the potential to become wings in insects. Parhyale hawaiensis, the crustacean we chose for our study (Fig 1), provided a great “model” crustacean for our investigation because their dorso-ventral body plan is very similar to that of insects, which makes comparisons between the two much simpler.
Fig 1. The crustacean Parhyale hawaiensis.
We started our search for wing homologs in Parhyale by identifying structures that are dependent on the gene vestigial (vg). vg is a critical wing gene in insects and has often been used for the molecular identification of wing homologs. We looked at expression and function of vg in Parhyale and noticed something striking. First, vg is expressed in both the tergal edge and the proximal leg segments. Second, when we knocked-out the function of vg via CRISPR/Cas9 genome editing, we saw that the development of BOTH of these tissues (tergum and proximal leg, related to insect pleuron11) was disrupted (Fig 2). We expanded our expression and function analyses to two more insect wing genes, nubbin (nub) and apterous (ap) and saw a similar outcome – these genes are expressed and/or function in both tergum and proximal leg segments (Fig 2). We were curious how big the overlap was between genes that function in wing development (wing gene network, WGN) and genes that function in tergum and proximal leg development of crustaceans, so we investigated the expression of a few additional wing genes in Parhyale. Many of these genes were also expressed in the tergum and proximal leg of Parhyale, and one of these genes, optomotor-blind (omb), showed impressive expression pattern overlap with the functional and expression domains of vg, nub, and ap (Fig 2).
Fig 2. The functional domains of vg, nub, and ap and expression domain of omb in Parhyale. Abbreviations are as follows: te, tergum; co, coxa; cp, coxal plate; gi, gill; ba, basis.
Through these investigations, we were able to show that a gene network similar to the WGN operates in both the tergal edge and proximal leg of Parhyale, suggesting that the evolution of this network precedes the emergence of insect wings. It also seems that both of these structures qualify as candidates for wing homologs of a crustacean. When we compare these structures to those that have been identified as wing serial homologs in the wingless segments of insects, we see a striking similarity; two separate tissues dependent on wing genes, one of tergal and one of pleural/proximal leg-related identity (Fig 3). The similarity between the wing-related structures in insects and crustaceans appears to point to a dual evolutionary origin of the insect wing and suggests that insect wings evolved through the merger of two previously distinct structures.
Fig 3. The evolutionary relationship among wing homologs. Blue and yellow represent tergal and pleural wing homologs respectively.
An aside about terminology: Historically, tissues related to wings on non-winged segments (either in insects or crustaceans) have been referred to as “wing homologs”. We are starting to see that this terminology is problematic especially when you consider the evolutionary order of the emergence of these structures. It seems that the “ancestral state” for wings is really two separate, previously existing structures in the form of tergum and pleuron (or ancestral proximal leg segments). Only in the winged segments of insects do these two previously separate structures seemingly merge to form the wing (Fig 3). Therefore, more accurate terminology for the wing-related structures on non-winged segments might instead be “tergal serial homologs” or “pleural serial homologs” as this is more representative of the ancestral state for these tissues. After all, it is becoming increasingly apparent with recent studies that these “tergal” and “pleural” serial homologs provide an “evolutionary hotspot” for the development of morphological novelties including, but not limited to, beetle thoracic horns, tree hopper helmets, beetle abdominal gin traps, and wings12.
References:
Grimaldi, D. & Engels, M. S. Insects take to the skies. in Evolution of the Insects 155–187 (Cambridge University Press, 2005).
Clark-Hachtel, C. M. & Tomoyasu, Y. Exploring the origin of insect wings from an evo-devo perspective. Curr. Opin. Insect Sci.13, 77–85 (2016).
Tomoyasu, Y., Ohde, T. & Clark-Hachtel, C. M. What serial homologs can tell us about the origin of insect wings. F1000Research6, 268 (2017).
Clark-Hachtel, C. M., Linz, D. M. & Tomoyasu, Y. Insights into insect wing origin provided by functional analysis of vestigial in the red flour beetle, Tribolium castaneum. Proc. Natl. Acad. Sci. U. S. A.110, 16951–16956 (2013).
Medved, V. et al. Origin and diversification of wings: Insights from a neopteran insect. Proc. Natl. Acad. Sci. U. S. A.112, 15946–15951 (2015).
Elias-Neto, M. & Belles, X. Tergal and pleural structures contribute to the formation of ectopic prothoracic wings in cockroaches. R. Soc. Open Sci.3, 160347 (2016).
Linz, D. M. & Tomoyasu, Y. Dual evolutionary origin of insect wings supported by an investigation of the abdominal wing serial homologs in Tribolium. Proc. Natl. Acad. Sci. U. S. A.115, E658–E667 (2018).
Tomoyasu, Y. Evo–devo: The double identity of Iisect wings. Curr. Biol.28, R75–R77 (2018).
Clark-Hachtel, C. M., Moe, M. R. & Tomoyasu, Y. Detailed analysis of the prothoracic tissues transforming into wings in the Cephalothorax mutants of the Tribolium beetle. Arthropod Struct. Dev.47, 352–361 (2018).
Clark-Hachtel, C. M. & Tomoyasu, Y. Two sets of candidate crustacean wing homologues and their implication for the origin of insect wings. Nat. Ecol. Evol. (2020). doi:10.1038/s41559-020-1257-8
Bruce, H. S. & Patel, N. H. Insect wings and body wall evolved from ancient leg segments. bioRxiv (2018). doi:10.1101/244541
Linz, D. M., Hu, Y. & Moczek, A. P. From descent with modification to the origins of novelty. Zoology143, 125836 (2020).
A four year postdoctoral position in the lab of Alex Gould is now available. Previous work in the laboratory, using Drosophila, has shown that the neural stem cell niche plays a critical role in sparing the developing CNS from stresses such as nutrient restriction and hypoxia (PMID: 26451484, PMID: 21816278). We are now looking for a highly motivated researcher to identify metabolic interactions between neural stem cells and their niche during stress protection. The successful applicant will have access to state-of-the-art techniques such as single-cell sequencing, gene editing and metabolomics. They will also have a unique opportunity to utilize cryogenic mass spectrometry imaging, a new method recently developed in the laboratory for visualizing metabolism in tissues at single cell resolution (PMID: 32603009). Applications are particularly encouraged from candidates with molecular biology and gene cloning skills. Prior experience with Drosophila is useful but not essential. Examples of other projects ongoing in the lab can be found at www.agouldlab.com and at www.crick.ac.uk/research/labs/alex-gould. The successful applicant will have good organisational and communication skills and a PhD in a relevant area (or be in the final stages of completion).
In my first post a few months back, I talked about the need for working scientists to create new habits of mind by practicing the craft of being a writer. Since then, I took my own advice. I abandoned Twitter, helped folks in the lab to get five papers into the BioRxiv, and finally finished an essay I’ve been working on for two years (with luck, you can read it in Development soon…). Last week, though, I was reading an interview in the New York Times with the newest winner of the Nobel Prize for Literature, the poet Louise Glück, and I was inspired.
She said this: “Though I couldn’t always write, I could always read other people’s writing.”
I love this. Here’s a Nobel Laureate acknowledging that she couldn’t always write, acknowledging perhaps as well that she can’t always write. We can all relate. Any writer faces writer’s block, but in science there’s often a far more tangible reason for not being able to write: Not enough data to write a paper! So, what do you do? How do you keep your writing practice moving forward when there’s nothing pressing to write about? Glück gives us the answer: You read.
There’s a catch, though; you have to read like a writer. This is rule #4 of DevBiolWriteClub. Happily, starting to read like a writer is simple and quick. The hard part of course is that it only matters if you keep it up, day after day, for a long, long time. There are no shortcuts.
So, what does it mean to read like a writer? In my view, there are two components. The first one is simple. You just do the work, with intent, every damn day.
Here’s what this looks like for me: I wake up, get eggs and coffee, and settle into the New York Times for at least 30 minutes, often for an hour. I do this, seven days a week. Usually, I read the front section and the columnists. When the news is too ugly, I skip all that and plunge straight into Arts or Food, sometimes Travel. I even sometimes read the Style section; I will read any article about Prince Harry and Meghan in its entirety, so long as it’s written well. Then I’m off to work (just in the next room these days), where of course I read all day. Emails do not count, but papers certainly do. At my mid-afternoon coffee break, if I can’t find someone to talk to me, I usually read a book, science history mostly or popular science. Finally, at the end of the night, I read more. Now it’s purely for fun, but it still counts. Novels, short stories, biography, satire, history. I once read an entire book by Nick Hornby that was just about reading books. There must be 30 books in various states of read or unread stacked next to my bed. My wife hates this mess. Regardless, I read a book in bed before I sleep every single night.
What does your reading schedule look like? How much did you read yesterday?
Ask yourself: How does your time spent reading compare with your time on Twitter or Reddit or TikTok? (Or in my case playing my kids’ Xbox.) It’s probably obvious that we might carve out at least a little extra time for reading. Now, do a more challenging exercise: How did your reading time yesterday compare with your time planning, performing, or interpreting experiments? Would your career benefit from exchanging 25 minutes a day of lab time for reading time? Over the next few months, no. Over the next ten years, though? The answer is certainly yes.
Next, ask yourself, “what did I read today?” In fact, ask yourself this question every single day. It’s a 10 second step that will put you on the right path. It will instill a habit of noticing what you read; this is the second component of reading like a writer.
As this new habit matures, you’ll find yourself noticing what you read when you read it. Eventually, this will grow into not just noticing what you read but also noticing the writing as you read (that was a really well written sentence; that was not, etc.). The key to developing this habit is to avoid the normal scientist’s instinct of simply devouring the content of a paper, squeezing it for every possible insight. Instead, try to carve out a small part of your consciousness and keep it focused on seeing the writing.
This will be an unfamiliar way of reading for many, so some exercises might help develop the practice. I like to underline sentences I think are particularly well written. An exclamation mark in the margin is my shorthand to indicate that a sentence was underlined for the writing, not the content. If you get through a week of papers without ever noticing a great sentence, another exercise may be useful: Make it a habit to simply ask yourself at the end of each paper, “what was my favorite sentence?” then spend a few minutes answering yourself. Even when I read for fun, I do something like this: Dog-eared pages in books in my library indicate that hidden on this page, somewhere, is a sentence I really liked.
Ok, so now we know what we need to do. Read and notice what you’re reading. The next question, then, is what should you read? Scientific papers first and foremost. I tell my PhD students to maintain a steady diet of one paper per day (or seven papers per week). Now, this does not mean you spend over an hour each day deeply reading, analyzing and annotating each paper (i.e. don’t read each one as if you were preparing it for journal club). Just read it, start to finish. Note the parts you like and dislike. Notice the writing independently from the content. That 25 minutes I talked about? Use 22 of them to read the paper and three to think about the writing. Then you’re done. Until tomorrow.
Obviously, this regimen will not sustain you over the long term; you have to have variety. So, find a way to read some non-science writing every single day. This can be books, magazines, or newspapers. The key is to read something that is professionally edited, so there is at least some expectation that the writing is good. (Reddit, Twitter, and internet screeds do not count; good blogs do count.)
A student subscription to the NY Times is $1.88 per week with the LA Times and Washington Post being similar. Scientific American and National Geographic are 20 bucks a year for students. The Economist is a bit more, but most university libraries and even local libraries provide broad newspaper and magazine access. Used bookstores provide incredible value. There’s just no excuse. You have to read widely, and you have to at least try to notice what you’re reading. Do this every day, even if only for a few minutes.
Build this habit now, and in a few years, you’ll be a better writer. Again, I wish I could tell you it’d happen faster, but it won’t. Just do the work.
I’ll end with something I read in another great piece in the New York Times. The Pulitzer Prize winner Viet Thahn Nguyen wrote: “… people ask me what it takes to be a writer. The only things you have to do, I tell them, are read constantly; write for thousands of hours; and have the masochistic ability to absorb a great deal of rejection…” That last bit will sound immediately familiar to scientists. We’d all do well to make that first part seem familiar as well.
The Kodjabachian lab at the Institute of Developmental Biology of Marseille (IBDM) is seeking a young and talented postdoctoral scientist with strong background in cell and developmental biology, and a keen interest in integrative quantitative biology and interdisciplinary research. Our lab uses advanced imaging techniques (such as confocal videomicroscopy, super-resolution microscopy and 3D electron microscopy) to study the biology of ciliated epithelia at multiple scales.
In vertebrate ciliated epithelia, flows of biological fluids are powered by the coordinated beating of myriads of ciliaharbored by multiciliated cells (MCC). In recent years, the global MCC transcriptome has been decrypted in Xenopus, mouse and human. Through this project, funded by ANR, we now wish to elucidate the functional MCCproteome. The selected candidate will be in charge of testing the functional importance of candidates selected through proteomic screens currently running in the team. He/she will use Xenopus epidermis, inducible MCC culture, and mouse post-natal brain as models to elucidate the mechanisms underlying vertebrate MCC construction.
IBDM offers a vibrant, international, and interactive environment to study the fundamental principles of cell and developmental biology. IBDM is also part of the Turing Center for Living Systems (CENTURI), a large interdisciplinary program allowing rich collaboration with theoreticians, physicists and computer scientists.
The ideal candidate must hold a PhD for less than two years, and have skills in cell culture, cell imaging, molecular biology, and biochemistry. The position is opened for one year renewable up to 3 years starting as early as January 2021. Applicants must email a CV, a statement of interest and contact details for 2-3 references to Laurent Kodjabachian.
Location: The Francis Crick Institute, Midland Road, London
Contract: Full time
Salary: Competitive with benefits, subject to skills and experience
Vacancy ID: 15088
Short summary
We are seeking a highly motivated and collaborative postdoc in the area of human embryology and stem cell biology to join Professor Kathy Niakan’s laboratory.
The aim of the project is to characterise early lineage specification in early human embryos. We have recently identified several transcription factors and components of key signaling pathways that are highly expressed in epiblast cells of the developing human embryo, which we hypothesize may have an important function for the development of these pluripotent cells. We seek to understand the function requirement of these factors using a range of methods including cutting-edge single cell, imaging and genome editing techniques. Ultimately, this knowledge will provide fundamental insights into human biology and facilitate the development of conditions for the further refinement of implantation models and the establishment of novel human stem cells and stem cell-based models of development.
We seek candidates who are energetic, focused, and productive with a desire to work in a congenial, dynamic, and collaborative research environment. Good organisational, analytical, and communication skills are essential.
Project scope
Dr Niakan’s laboratory focuses on understanding the mechanisms of lineage specification in human embryos and the derivation of novel human stem cells. Details of research projects currently being undertaken can be seen at: http://www.crick.ac.uk/kathy-niakan
Research techniques used in the laboratory include: molecular biology, advanced microscopy and image quantification, human and mouse preimplantation embryo culture and micromanipulation, genome modification, genome-wide techniques including single-cell RNA-sequencing, multi-omics analysis and human trophoblast, embryonic and induced pluripotent stem cell derivation.
About us
The Francis Crick Institute is a biomedical discovery institute dedicated to understanding the fundamental biology underlying health and disease. Its work is helping to understand why disease develops and to translate discoveries into new ways to prevent, diagnose and treat illnesses such as cancer, heart disease, stroke, infections, and neurodegenerative diseases.
An independent organisation, its founding partners are the Medical Research Council (MRC), Cancer Research UK, Wellcome, UCL (University College London), Imperial College London and King’s College London.
The Crick was formed in 2015, and in 2016 it moved into a new state-of-the-art building in central London which brings together 1500 scientists and support staff working collaboratively across disciplines, making it the biggest biomedical research facility under in one building in Europe.
The Francis Crick Institute is world-class with a strong national role. Its distinctive vision for excellence includes commitments to collaboration; developing emerging talent and exporting it the rest of the UK; public engagement; and helping turn discoveries into treatments as quickly as possible to improve lives and strengthen the economy.
If you are interested in applying for this role, please apply via our website.
The closing date for applications is 16 November 2020 at 23:45.
All offers of employment are subject to successful security screening and continuous eligibility to work in the United Kingdom.
Cortical development involves a switch from the self-amplification of stem cells to the generation of neuron and glia by progenitors. A new paper in Development investigates the molecular control of mitosis in these two stages, using simultaneous labelling and gene knockout in clones in the developing mouse brain. We caught up the paper’s two authors Caroline Johnson and her supervisor Troy Ghashghaei, Professor of Neurobiology at the College of Veterinary Medicine at North Carolina State University, to find out more.
Caroline and Troy
Troy, can you give us your scientific biography and the questions your lab is trying to answer?
TG I did my graduate work mapping limbic circuits, focusing on connections between the basal forebrain/amygdaloid nuclei and the prefrontal cortices of macaque monkeys. Some of the results raised a number of developmental questions, which led me to pursue a postdoc in developmental neurobiology. Therefore, I did my postdoc work on adult neurogenesis and cortical development, which we have continued in my own lab since 2006. I am now a professor and my lab is currently focused on two main projects: (1) how neural stem cells undergo developmental transitions during distinct time points, and how perturbations of these transitions impact proliferation and differentiation in the forebrain and cortex; (2) how ependymal cells are formed from embryonic neural stem cells and how these fascinating and poorly studied cells regulate forebrain homeostasis during adulthood and aging. We use a genetic approach in understanding the functions of various factors, and employ interdisciplinary tools to identify, characterize and test various phenotypes in the two projects.
Caroline, how did you come to work with Troy and what drives your research today?
CJ When I was an undergraduate at UNC Chapel Hill, I volunteered with the veterinarians at the Duke Lemur Center, and worked at Duke studying the diversity of mouse lemur species. I then worked as a technician at Harvard, which sparked my interest in neuroscience research. When I was looking for graduate programmes, I wanted to move back to North Carolina because there are a lot of great research opportunities here and I could be closer to my family. I was also potentially interested in veterinary medicine research, which led me to look at graduate programmes with the veterinary school at NC State University [NC State]. When I heard about the projects in developmental neuroscience research occurring in Dr Ghashghaei’s lab, I contacted him and enrolled in the Comparative Biomedical Sciences programme. Cortical development is an amazing field. The sensitivity of the cortex to disruptions in cell division and the paradigm of its development permits us to ask questions about basic development, comparative development and cell proliferation, and gives us greater insight into how this fascinating structure has developed and evolved.
How did you come to study Sp2 and what was the main question your current paper was aiming to answer?
TG My colleague Jonathan Horowitz and his lab were researching the function of Sp2 in cancer cells when I first arrived at NC State. Sp family members have a fascinating genomic organization and they are all involved with important aspects of organismal development. When we began this project, Sp2 was the least studied family member. In collaboration with the Horowitz lab we found that Sp2 is highly expressed in neurogenic regions of the postnatal and embryonic mouse forebrain. This led a previous graduate student in the lab, Huixuan Liang, to investigate what happens when Sp2 is deleted during neurogenesis at the embryonic and postnatal stages of forebrain development. She found that Sp2 is required for timely progression through mitosis within neurogenic niches, and the results of that work were published in Development in 2013. That is when Caroline joined the lab and the current paper is a summary of all the work she has done over that last few years. It is important to note that the use of MADM technology was instrumental in this work and our interactions with my friend and colleague Simon Hippenmeyer (a co-author on the 2013 paper) were critical in the initial stages of the project.
CJ My major focus was to dynamically investigate mitosis to understand how its timing was affected by loss of Sp2, as the previous project has identified a defect in M-phase progression. Additionally, I wanted to look at earlier stages of corticogenesis prior to the transition to neurogenesis when the stem cell pool is expanding. A very important finding that emerged from our work has been the revelation of phenotypic differences between bulk and sparse genetic deletion strategies. The complex genetic models we used revealed that bulk deletions can cause major non-autonomous effects that may mask the cell-autonomous role of a protein. By using sparse deletions, we are able to measure in detail genotype-phenotype associations.
Micrograph of a coronal section through the forebrain of a mosaic analysis with doublemarkers (MADM) mouse at birth. MADM recombination was restricted to the dorsal telencephalon (hence cortex), which labels progenitors and their offspring sparsely, and in distinct colours (here in an artistic rendition).
Can you give us the key results of the paper in a paragraph?
CJ Essentially, we found that Sp2 is required for neurogenesis during a distinct time point of cortical development. Surprisingly, Sp2 is dispensable for early stages of corticogenesis, when stem cells are amplifying and the switch to neurogenesis occurs, but later, when the production of upper layer neurons begins, loss of Sp2 affects the timing of mitosis and ultimately results in the decreased production of neurons.
Do you think that Sp2 acts primarily in neural progenitor cell or intermediate progenitor division when promoting the production of upper layer neurons?
CJ I think that ultimately disruption of mitosis in the neural progenitor population results in the decreased production of intermediate progenitor cells, but it is also possible that disrupted mitosis in the mother cell has consequences for the proliferative capacity of intermediate progenitor cells. An important next step would be to look at the timing of mitosis in the neural and intermediate progenitor populations at multiple neurogenic stages to see how their populations and mitotic timing are affected. Additional experiments specifically deleting Sp2 from the intermediate progenitor population would also be interesting.
TG While we did not distinguish between the two modes of terminal divisions in our study, we suspect both are affected. However, one has to do the experiment to answer the question directly. The results in our current paper reveal stronger effects on large clones and upper layer-specific sensitivity when Sp2 is deleted at sparse levels, which suggest both types of terminal divisions are likely affected in the absence of Sp2.
Do you have any idea about the transcriptional targets of Sp2 that might ensure timely mitosis?
CJ Recent studies of Sp2-dependent transcription have indicated it is involved in multiple pathways and may require different co-factors. It is unclear what the transcriptional activity of Sp2 is outside of cell lines and in developing tissues, whether or not it interacts with these potential co-factors within the developing cortex, and/or if it is playing a non-transcriptional role at one of these stages. Sp2 is known to interact with the nuclear matrix and may be regulating gene expression through a process independent of transcriptional regulation.
TG Our lab has been pursuing questions related to upstream regulation of Sp2 and downstream targets of this interesting protein, but more work is needed.
When doing the research, did you have any particular result or eureka moment that has stuck with you?
CJ Realizing that larger clones had a stronger phenotype in response to loss of Sp2 was definitely exciting, as it indicated that the clones that were expanding throughout neurogenesis were most affected (similar to our results in the other experiments). The smaller clones, which likely reflected lineages that immediately entered neurogenesis, were not strongly affected.
Working with animal models is always more complicated than you would hope
And what about the flipside: any moments of frustration or despair?
CJ Of course, working with animal models is always more complicated than you would hope, and the early timepoint experiments were surprising at first because Sp2 has a known role in cell proliferation. However, doing the additional experiments with bulk deletion and an additional Cre driver line helped to reveal that we really weren’t seeing an effect at this early stage of cortical development.
So what next for you after this paper?
CJ I am working with Dr Ghashghaei on projects in the lab related to my previous project. In terms of the future, I’m interested in exploring scientific writing or clinical research careers to help advance biomedical research.
Where will this work take the Ghashghaei lab?
TG We are moving forward with a number of projects that continue to interrogate mechanisms that regulate the transitions that NSCs and NPCs in the forebrain go through as development proceeds.
Finally, let’s move outside the lab – what do you like to do in your spare time in Raleigh?
TG I have been playing soccer (football to the rest of the world outside America) for a long time. Playing with old friends as well as coaching and scouting for some of the local clubs forms much of my time outside the lab. In addition, my daughter is a gymnast in college – so I spend quite a bit of time with my wife going to her meets.
CJ Raleigh is a beautiful city and the veterinary school is located next to the art museum and greenway, so I like to run at the trails there. I also enjoy cooking and spending time at my parents’ farm.
Postdoc position is available at the Max Delbrück Center (MDC, Berlin, Chekulaeva lab). ALS is a neurodegenerative disease affecting motor neurons, i.e. neurons that control skeletal muscle contraction to produce motion. Despite heterogeneous etiology, ALS is characterized by abnormalities in RNA metabolism. The successful candidate will work with the collection of ALS patient-derived hiPSCs and hiPSC-derived motor neurons to investigate how changes in RNA metabolism contribute to the mechanism of neurodegeneration. The project will reply on a combination of omics (transcriptomics, Ribo-seq, CLIP-seq), computational, CRISPR/Cas-mediated gene editing and imaging approaches and will involve a collaboration with international partners, contributing different expertise to the project, including computational analysis, in vivo ALS models and clinical research.
Ideal candidate should have experience in cell culture and molecular biology techniques, interest in RNA biology and neurodegeneration. Experience in hiPSC work and RNA methods is an advantage. To apply, please send your motivation letter and CV with contact details of at least two referees to marina.chekulaeva(at)mdc-berlin.de
Recommended reading:
von Kuegelgen N and Chekulaeva M# (2020). Conservation of a core neurite transcriptome across neuronal types and species. WIREs RNA 14:e1590. http://dx.doi.org/10.1002/wrna.1590
Ciolli Mattioli C., Rom A., Franke V., Imami K., Arrey G., Terne M., Woehler A., Akalin A., Ulitsky I., and Chekulaeva M. (2018). Alternative 3′ UTRs direct localization of functionally diverse protein isoforms in neuronal compartments. Nucleic Acids Research, https://doi.org/10.1093/nar/gky1270
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