The Company of Biologists’ journals – Development, Journal of Cell Science, Journal of Experimental Biology andDisease Models & Mechanisms – offer Travelling Fellowships of up to £2,500 or currency equivalent to graduate students and post-doctoral researchers wishing to make collaborative visits to other laboratories. These are designed to offset the cost of travel and other expenses. There is no restriction on nationality.
The deadline for the current round of applications is tomorrow – 31 August!
Have you heard of an animal that can lose most of its body tissues and the remnant tissues aggregate to regenerate the lost parts and recovery its original form?
Do you know an animal that can quickly colonize marine surfaces by asexual reproduction, just like weed would in terrestrial environments ?
Do you know an animal that can disperse to new locations when small portions of its body separate and move away from the rest?
These descriptions may remind you of characters from science fiction stories, but these are real characteristics of colonial animals. Animals colonies are composed of discrete multicellular units (e.g zooids, polyps), that are physiologically interconnected and undergo clonal replication maintaining an identical genotype throughout all of their components (Hughes, 1989; Jackson & Coates, 1986) . This includes a number of marine and freshwater animals, such as many corals and hydroids, bryozoans, some hemichordates and some ascidians (a group within the subphylum Tunicata). One of the main projects in the laboratory is to study the evolution of colonial life strategyin ascidians, in which coloniality evolve several times.
I am a PhD student in Prof. Federico Brown’s laboratory (http://zoologia.ib.usp.br/evodevo2/) in the Department of Zoology at the University of São Paulo. We are located in a subtropical area in the south of Brazil, in a huge metropolis 100 km away from the ocean. In fact, our lab is located next to a small forest reserve on campus that is reminiscent of the Mata Atlantica Forest (a hotspot of biodiversity), from the laboratory’s windows, we can see a great diversity of birds, insects, spiders and sometimes even monkeys (Fig.1).
Fig. 1 Location of the Federico Brown’s laboratory and ascidian collection sites. (A) Location of the University of São Paulo. (B) A port in Santos city where we collect and grow the colonial tunicates. (C) View of the laboratory at the University of São Paulo.
Our work in the laboratory begins with the collection of tunicates from the ocean. We travel by car to close coastal cities, including São Sebastião (4h away) and Santos (1h away) (Fig. 1B). We collect the tunicates from pilings and floats in the port marinas. The colonial species are carefully collected and attached to glass slides using thread (Fig. 2A). The slides are placed in slide boxes, with open windows on both sides to allow water circulation, and the boxes are hung to the dock with ropes. After two weeks, the colonies grow to cover the slides. Therefore attached tunicates are cleaned, transported to the aquarium system, and are ready for use in experiments (Fig. 2).
Fig. 2 Procedures to attach and cultivate ascidians. (A) Colonial ascidians are attached with a thread to a glass slide. (B) Colonial ascidians on the glass slides are placed in racks for culturing. (C) At our field sites, glass slides with ascidians are placed in slide boxes with windows and hung from the dock to allow them to grow in the ocean
For my PhD project, I am working with the genus Symplegma, a member of the family Styelidae, in which coloniality arose at least twice from solitary ancestors. Symplegma is the sister genus to the botryllids (Botryllus and Botrylloides), a group of highly integrated colonial species that undergo weekly cycles of asexual development (Brown et al., 2009). Symplegma has less integrated colonies and characteristics more similar to the solitary species. Thus it is an interesting genus to study the evolution of coloniality.
Symplegma, as other colonial ascidians, has internal fertilization and brooding, with embryos that are incubated for several days to weeks before the tadpole larvae are released. The tadpole larva have a brief period of swimming and settle rapidly (Fig. 3A). During settlement, the larvae undergo metamorphosis, in which most of the tail structures are resorbed and the mouth rotates close to 90º to the dorsal side, changing from a tailed swimming larva into a sessile filter feeder (Fig. 3).
Fig. 3 Stages of Symplegma development. (A) Newly released larva of the species Symplegma rubra. (B) Settled larva in the process of metamorphosis, with extended ampullae. (C) Later stage of metamorphosis, where the primary ampullae have fused. (D) First zooid and bud (arrowhead) formed after metamorphosis. (E) Symplegma brakenhielmi colony. (F) Symplegma rubra colony.
During metamorphosis, the ampullae extending a symmetrical pattern around the first zooid (Fig. 3B). The ampullae are peripheral pouch-like structures of the blood vessel system, essential for communication of the colony with its environment. Then ampullae continue to extend and, interconnect to form the primary net of blood vessels, in which the blood circulate constantly (Fig. 3C). Then this system of vessels grows forming more vessels that connect the zooid and the first bud (Fig. 3D).
Inside the vessels, specialized blood cells circulate, constantly coordinating biological processes between the zooids of the colony (Video 1).
For example, the circulatory cells are key to the clonal formation of new buds and the coordination of death of old zooids. New buds can be formed in two locations, either at the lateral epithelium of the adult zooid or along blood vessels that are far from adult zooids (Fig. 3E-F).
While some colonial styelids have highly integrated colonies with coordinated cycles of degeneration and regeneration of zooids, Symplegma is much less integrated and coordinated. We are interested in how developmental and regenerative processes differ between species with different degrees of coordination and integration. For example, we conduct experiments to observe whole body regeneration by removing all the zooids and buds retaining only the blood vessels of the original colony. Immediately after surgery, the blood coagulates and circulation in the remnant vessels stops. Twelve hours after the surgery, blood circulation is restored without any zooids or heart to pump the blood. Presumably, this circulation is caused by vessel contractions (Video 2).
Next, the remaining vascular tissue aggregates and form a mass, in which new zooids arise. Ten days after surgery a complete functional colony has regenerated (Fig.4).
Fig. 3 Regeneration in a Symplegma brakenhielmi colony. (A) Colony before ablation, in which a fully differentiated zooid is shown. (B) Colony immediately after ablation, zooid and buds were removed (asterisks) and only the vascular tissues remain. (C) Day 2 after ablation, vascular tissues have aggregated and new buds are observed at stage 5 (arrowhead); asterisk shows the scar of the surgery. (D) Day 5 after ablation, the vascular tissues form a mass and a bud (arrowhead) continues to develop (stage 7). (E) Day 10 after ablation, the new zooid is fully differentiated (stage 9.2). Scale bar is 500 µm. (Edited from Gutierrez & Brown, 2017).
These results suggest that the vascular tissue has the capacity to rearrange itself and regenerate new zooids. Our results show that Symplegma colonies act like self-regulating systems that have the ability to rearrange its components (blood vessels and blood cells) after perturbations to regenerate damaged or lost parts. Due to the presence of replaceable zooids, the colonial life history allows for the recovery of lost parts by regeneration, fast colonization of marine substrates, and high survival rates after predation or weather-related disturbances. These colonial animals are like superorganisms!! They show amazing developmental mechanisms linked to coloniality.
If you would like any more information about their life history and how to work on them, just ask us in the comments or via email [as.gutierrez57@ib.usp.br].
References
-Brown, F. D., Tiozzo, S., Roux, M. M., Ishizuka, K., Swalla, B. J., & De Tomaso, A. W. (2009). Early lineage specification of long-lived germline precursors in the colonial ascidian Botryllus schlosseri. Development (Cambridge, England), 136(20), 3485–3494.https://doi.org/10.1242/dev.037754
-Gutierrez, S., & Brown, F. D. (2017). Vascular budding in Symplegma brakenhielmi and the evolution of coloniality in styelid ascidians. Developmental Biology, 423(2). https://doi.org/10.1016/j.ydbio.2017.01.012
-Hughes, R. (1989). A Functional Biology of Clonal Animals. New York: Chapman and Hall.
-Jackson, J. B. C., & Coates, a. G. (1986). Life Cycles and Evolution of Clonal (Modular) Animals. Philosophical Transactions of the Royal Society B: Biological Sciences, 313(1159), 7–22. https://doi.org/10.1098/rstb.1986.0022
Very excited to invite applications from post-doctoral researchers to join my lab to work on a Leverhulme Trust- funded project to look at the mechanisms regulating branching in Selaginella kraussiana. I would like to use a candidate gene approach, looking at Selaginella PIN and TCP function. I have written a bit about the project here, and you can apply here.
When people digest food, the flow of fluids and digestive enzymes to the gut is critical. Until recently, researchers had marvelled at the incredibly complex system of ducts that transports a stream of enzymes and mucus from the pancreas to the gut. Astonishingly, a research project led by Professor Grapin-Botton has revealed that the ducts are created similar to river beds. This new knowledge may lead to improving treatment for people with cystic fibrosis and diabetes.
Most people associate transport with roads, rivers or rails. In nature, transport is equally vital. Trees have a transport system in their roots, branches and leaves, and humans have many transport channels such as nerve fibres and lung bronchioles. Many of these structures are nearly identical from person to person. However, this does not apply to the transport ducts between the pancreas and the gut, which are essential for efficient digestion. A Danish research project has now solved the enigma of how the ducts are created to transport mucus, enzymes and chemical substances.
“The transport channels from the pancreas to the gut are critical for digesting food and neutralizing acidic gastric juices. Because efficient transport is essential, we wondered why the ducts vary from person to person. Our new results show that the channels can change similarly to a river bed during fetal life. The channels with the greatest flow appear to widen, whereas others run dry and disappear. This knowledge may help us to treat people with cystic fibrosis and some forms of monogenic diabetes associated with cystic ducts, who have such transport problems,” explains Anne Grapin-Botton,
A surprising result
To map how the ducts inside the pancreas are formed, the researchers marked the ducts with fluorescent antibodies, which enabled them to see when a duct was formed and its connection to others. The researchers monitored the development of the pancreas in mice.
“During organ development in fetuses, the ducts are initiated from small holes. These small holes connect and fuse together, thereby creating many ducts that develop into a complex network. It resembles a town with a labyrinth of streets. What fascinated us was how, from this labyrinth, a simpler treelike structure emerged at birth.”
To keep track of the high volume of data and to identify how the network of ducts changed, the researchers teamed-up with Kim Sneppen, a professor and physicist from the Niels Bohr Institute, University of Copenhagen. Svend Bertel Dahl-Jensen, their PhD student, pulled together the threads and uncovered the secrets of the labyrinth.
“We decided to adapt the programs used to model road, rail or internet networks, and the picture that emerged once we inputted the data into the computer reminded us of something familiar: a river system. And indeed, going back to the laboratory, we found that as soon as the ducts were formed they secreted juice. We think that this creates a flow of fluid towards the intestine already in fetuses. Some ducts widen, while others run dry and disappear.”
Pancreatic ducts (as well as the surrounding duodenum) are shown in green (stained for β-catenin) and the islets of Langerhans appear in red (stained for insulin). Image Credit: Dror Sever
Ducts collapse
The study showed that the cells from the collapsed ducts did not simply disappear. They are likely recycled to widen existing ducts. This may turn out to be important for medicine.
“People with cystic fibrosis or with certain forms of monogenic diabetes have problems in the pancreatic ducts. For diabetes, we do not know why diabetes and enlarged ducts are associated when certain genes are mutated.”
People with cystic fibrosis have defective pancreatic ducts. This results from mutations in a gene that codes for a channel enabling fluid secretion inside the ducts. The researchers demonstrated that the secretion defects may start very early in fetuses and their work may lead them to consider earlier treatment.
“We would now really like to understand why people whose pancreatic ducts have collapsed are more likely to develop diabetes. One hypothesis we are pursuing is that they make less beta cells secreting insulin. These cells are initially formed in the ducts. We are now studying this in mouse models and in miniature human pancreas (organoids) made from stem cells in 3D culture.”
In our recently published paper https://elifesciences.org/articles/34880, we report that the transcription factor Pitx2c has an unexpected role during gastrulation, where it acts cell non-autonomously to promote mesendodermal cell migration required for axis extension in zebrafish.
“It is not birth, marriage or death which is the most important time in your life, but gastrulation.
– Lewis Wolpert, 1989
Undoubtedly, gastrulation is a critical time during development, as the entire body plan is defined by what happens at this stage. Cells must undergo intricate and complex movements to generate the three germ layers and end up in the correct location to give rise to all of the parts of the body. Not only is it an absolutely beautiful event to observe, it is also an essential developmental process that is well-suited for probing important questions surrounding cell behaviour during migration and embryonic patterning. This process is especially clear in the zebrafish embryo – its optical transparency and amenability to live imaging allow one to attain single-cell resolution to examine cellular behaviours in real-time.
How it all started…
When I joined Didier Stainier’s lab as a postdoc, I wanted to focus on questions surrounding cardiac laterality in zebrafish. While it has been known for over 20 years that the transcription factor Pitx2c is a critical player in defining the left side of the body, many questions surrounding how Pitx2c directs this process remain to be explored. Around this time, Didier was in contact with Patrick Blader from the Centre de Biologie du Développement, Université Paul Sabatier in Toulouse. Patrick’s lab had recently generatedzebrafish mutant alleles in pitx2, and he generously shared his line with us.
We started analysing these mutants, and at first, I was rather disappointed that we did not see any defects in cardiac laterality! However, when we looked at the phenotypes in embryos lacking both maternal and zygotic (MZ) Pitx2 function, we observed many embryos at 24 hours post-fertilization with shorter bodies and somite defects. These phenotypes were reminiscent of many of the gastrulation mutants recovered in ENU screens, and so we began exploring the role for maternal and zygotic Pitx2c function in more detail.
What we learned…
We first questioned whether any patterning defects were present in MZpitx2c mutants during gastrulation and early somitogenesis and looked at the expression of many genes by in situ hybridization. While the different germ layers were present, it was obvious that the cells were not in their correct location. For example, we observed that the cells giving rise to the notochord were located in a wider domain than in wild-type embryos. We also found that at late gastrulation, mesendodermal cells looked rather disorganized, arguing that cell migration was likely affected in these mutants.
Gastrulation movements in zebrafish have been very well described. While epiboly spreads the cells of the epiblast down around the yolk, mesendodermal precursors separate from the epiblast and migrate away from the margin via internalization movements. Internalization is followed by convergence and extension movements that mediolaterally narrow the embryo, while elongating them along the anterior-posterior axis. We first focused on assessing convergence and extension movements in the mutants since they presented phenotypes suggestive of defects in these cell behaviours.
To test whether convergence and extension movements were affected in the MZpitx2c mutants, we photoconverted lateral mesendodermal cells and tracked their migration over time. These experiments suggested that both dorsal convergence and anterior extension were reduced. Similarly, we observed that the distance between the prechordal plate and the notochord at the 1 somite stage was reduced in MZpitx2c mutants compared to wild types, and when we looked at cell morphology within the notochord of mutants, we found that the cell shapes were rounder and failed to elongate mediolaterally as in wild-type embryos. These data suggested to us that Pitx2c functions to promote convergence and extension movements.
Previous work from our group and others has described the movements of endodermal cells. In this population of cells, early gastrulation movements undergo a ‘random walk’ motion to spread endodermal cells across the embryo; at late gastrulation, endodermal cells rapidly increase their speed and migration trajectories, becoming straighter and oriented towards the midline to form the endodermal sheet. When we examined these behaviours in MZpitx2c mutants, we observed that the transition between random walk motion to oriented, persistent migration was blunted. Taken together, our data indicate that cell migration behaviours during late gastrulation are strongly disrupted in the absence of maternal and zygotic Pitx2c function.
We then performed transplantation assays, which really gave us critical insight into the role of Pitx2c. In these experiments, we transplanted mesendodermal cells that expressed LIFEACT-GFP into unlabelled host embryos, allowing us to analyse cell migration behaviours at single-cell resolution. What was especially striking were the observations that wild-type cells that were transplanted into MZpitx2c hosts sent out fewer projections and their morphology was flattened. These key observations indicated that Pitx2 is required cell non-autonomously to promote migration behaviours of mesendodermal cells.
Movie: WT cells expressing LIFEACT-GFP were transplanted into WT (left panel) or MZpitx2c mutant (right panel) hosts. Transplanted WT cells exhibit increased surface area and extend fewer protrusions that appear more actin-dense in mutant hosts compared to WT hosts.
At the same time, we were also analyzing microarray data from MZpitx2c mutants and in embryos where we had injected pitx2c mRNA at the 1-cell stage. One of the top hits in these analyses was a gene encoding the chemokine ligand Cxcl12b. A few years ago, the Schilling and Kikuchi labs showed that mesodermal expression of cxcl12b (or sdf1b) was important to coordinate and guide the movements of the endoderm, which express the receptor gene cxcr4a. They also proposed that Cxcl12b/Cxcr4a signaling promotes integrin-mediated adhesion for coordinated mesendodermal cell migration. Furthermore, Cxcl12b/Cxcr4a signaling regulates the formation of filopodial processes in gastrulating mesendodermal cells.
Together, these data fit very nicely with the phenotypes we had observed in MZpitx2c mutants, and so we focused our analyses of these pathways. Indeed, we found disrupted expression of cxcl12b and the integrin subunit gene itgb1b, as well as altered deposition of Fibronectin between mesendodermal cells. Therefore, these data suggested that Pitx2 functions upstream of chemokine-dependent changes in adhesion to the ECM to influence cell migration.
What does it mean?
Pitx2 is a transcription factor that plays diverse roles in many tissues and developmental contexts. In humans, mutations in PITX2 coding regions lead to Axenfeld-Rieger syndrome, while promoter/enhancer mutations are associated with atrial fibrillation. Despite these clinically relevant syndromes, few downstream pathways have been identified. In our paper, we describe a role for Pitx2c where it promotes convergence and extension movements during gastrulation. Using transcriptomic analyses of pitx2c gain- and loss-of-function embryos, we identify transcriptional changes in genes involved in chemokine-ECM interaction and signaling.
We hypothesize that the early function of Pitx2 during gastrulation is evolutionarily conserved. Recent work from the Stern and Viebahn groups has shown that Pitx2 expression precedes the formation of the primitive streak in chick and rabbit embryos. We were also very excited to find expression of pitx2 in single-cell RNAseq datasets of early gastrula stage mice and frogs, suggesting that Pitx2 is also playing an early role in these species.
These studies raise the question as to whether similar mechanisms downstream of Pitx2c are at play in other developmental contexts. As the Nodal-Lefty-Pitx2 cascade appears to be conserved at both the onset of gastrulation and during the establishment of left-right identity, it will be exciting to explore whether the downstream pathways we identify here are conserved in other contexts.
It’s an age-old mystery of the heart: do opposites attract, or will like do better with like? We can now answer this pressing question, at least for Drosophila cardioblasts: cells prefer to ‘swipe right’ on a shared transcriptional profile, but the resulting relationships are stronger if there are some unattractive alternatives around to remind them to love the one they’re with.
To put that in more scientific terms, in order to build complex structures that perform versatile functions, biological systems need to be able to specific and precise cell-cell connections. Yet the question of how cells find the right partners as organs form generally remains poorly understood. In our recently published work (Zhang et al., 2018), our team has uncovered some of the secrets of how cells make the perfect match.
The Drosophila heart tube is constructed from two parallel lines of connected cardioblasts in the developing mesoderm, initially separated by over 100mm. The cardioblasts migrate together and create the heart tube during stage 16. The cardioblasts have distinct subtypes: Tinman-positive cells that form the heart lumen and valves; and Seven-up-positive cells that form the ostia. The Drosophila cardiogenesis ‘dating algorithm’ has Tinman and Seven-up-positive cardioblasts lined up in a repeating 4-2 pattern (Figure 1). As the contralaterally opposing lines of cardioblasts come together, they only match up with cells of the same type (Figure 1). We set out to investigate: how does this happen, and why?
Figure 1: Schematic of embryonic Drosophila heart formation. As the cardioblasts approach each other (left), their filopodia interact (middle), and eventually form precisely matched boundaries (right). Tin-: Tinman-positive cardioblasts (CBs); Svp-: Seven-up- positive cardioblasts (CBs).
Primary ‘matchmaker’ Shaobo Zhang, as part of an undergraduate research project, had the job of figuring this out. He was working under tough conditions: less than a year old, the lab had few reagents and no fly room. Nevertheless he got his hands on a Hand::GFP line, which expresses a marker for cardioblasts in the Drosophila embryo, and developed cell tracking software to see how the cells migrate during heart formation (Figure 2). The project proved compelling enough to persuade Shaobo to join the lab (https://mbi.nus.edu.sg/timothy-saunders/) for his PhD studies, seemingly undaunted that the PI was a theoretical physicist. (It probably helped that by then we had a mini fly room – albeit with three levels of security to stop any flies escaping, Figure 3).
Shaobo noticed that – rather like competitors on Love Island – cardioblasts could change the partner they coupled up with quite abruptly. As the team looked more carefully, we realised that cells were sampling their local environment using filopodia protrusions. However, not all cells were equally good at finding their partners precisely. The best matched cells were at the boundary between the Tinman- and Seven Up- positive cardioblasts.
Figure 2: Cell tracking of cardioblasts with home-developed tracking software. On right, the green lines represent the cell tracks. Note that as cells approach their counterparts the tracks move more.
Figure 3: Our mini fly room (right) with three security levels to stop flies escaping (left)
But what factors helped cells decide which of the opposing cells was the right one for them? We notice that the filopodia forming strong connections were generally from the Tinman-positive cells. In contrast, the filopodia interactions between Seven Up-positive cells were distinctly unromantic, and rather more like Neymar and Ronaldo having a fight – a lot of arm-waving and drama, but no meaningful contact.
Shaobo reasoned that cell-cell adhesion molecules may be differentially expressed in cardioblasts to facilitate the selective filopodia adhesion. At this point he turned to the literature, as neurobiologists have been investigating neuronal cell matching for years and a range of known “matching” molecules are known, though the dynamic mechanisms through which they act are not fully understood.
Figure 4: Antibody staining of Fas3 (green), Ten-m (magenta) and Tinman (white) in heart cells during stage 16.
Performing a mini-screen of these targets, we found that Fasciclin III (Fas3) stood out. Fas3 is a homophilic adhesion molecule (Figure 4), which was more highly expressed in the Tinman-positive cardioblasts. Perturbing the expression pattern of Fas3 resulted in perturbations of their filopodia binding activities, leading to increased cell mismatch.
At this point, it looked like we had found the molecule driving cell matching (a bit like alcohol at a student party). However, when we looked at fas3-/- mutants we noticed only a small defect in cell matching (unbelievably, dating can also occur sober). Returning to our screen results, we noticed that the adhesion molecule Ten-m (also known as Teneurin-m or Tenascin-m – sometimes naming conventions really need to be sorted out) was upregulated in Seven-up positive cells (Figure 4). After some painful crosses, Shaobo produced the double mutant of Fas3 and Ten-m, which, thankfully, had a significant matching phenotype. Therefore, it appears that heart cells use two (partially redundant) adhesion molecules to ensure they find the right partner.
But how is this differential expression pattern genetically regulated? To answer this, we turned to Dr David Garfield at Humboldt University in Berlin (https://www.garfieldlab.org/). By looking at putative enhancers specific to mesodermal and neuronal tissue, he identified potential tissue-specific enhancers for Fas3. Shaobo made reporter lines to test whether these distinct regions correspond to the specific expression patterns for Fas3. Thankfully they did, with specific expression in cardioblasts (with differential expression in distinct cell types) and neurons. So – for cardioblasts anyway – the odds of pair-bonding are partly a matter of genetic destiny.
This project was a lot of fun as we explored how both mechanical and genetic mechanisms interplayed to regulate the precise cell matching and help forming the properly structured heart. Given the conservation of many of the genes involved in early heart formation, we are hopeful that this will have relevance to vertebrate systems. More interestingly, this shows a simple but potentially general dynamic mechanisms of constructing specific cell-cell connections in biological systems. We’ll keep you posted if we crack the human relationship code too.
Reference
Zhang, S. et al. (2018) ‘Selective Filopodia Adhesion Ensures Robust Cell Matching in the Drosophila Heart’, Developmental Cell, 46(2), p. 189–203.e4. doi: 10.1016/j.devcel.2018.06.015.
All life requires energy. For early metazoan development, demand is especially high, as the transition from a single cell to a complex, multicellular organism requires a massive energetic input. In the earliest stages of development, however, an organisms’ inability to feed poses an apparent problem: how is the energy necessary to drive development obtained? In most species, this problem is solved via maternal contribution. In Drosophila, for example, newly laid embryos contain abundant neutral lipids that are broken down to generate much of the energy necessary to drive embryogenesis: prior to egg laying, these neutral lipids are deposited into the egg by the mother, in the form of lipid droplets (LDs). While the critical roles of LDs in energy homeostasis have been investigated for decades, recent research has demonstrated that LDs may serve moonlighting functions beyond lipid metabolism, including roles in protein handling.
Early Drosophila embryos contain an abundance of maternally deposited lipid droplets. 3D rendering was generated from confocal images and shows a surface view of an ~2hr old embryo stained for nuclei (blue) and lipid droplets (green).
The lipid droplet proteome is vast, containing a variety of proteins. Many of these proteins, as one might expect, have central roles in lipid metabolism. However, what may come as a surprise, is the observation that several LD-resident proteins have known functions outside of lipid homeostasis. For years, such proteins were thought to be mere contaminants of a “dirty” LD purification procedure. More recently, however, a growing field of research has demonstrated that such localization is not only real, but also can have profound impacts on protein abundance and function.
Our story began just over a decade ago when our group and their collaborators identified, with high confidence, hundreds of proteins localized to the surface of LDs in early Drosophila embryos1. Of particular intrigue was the identification of a subset of histone proteins, namely core histones H2A and H2B as well as the Drosophila H2A variant H2Av. A priori, the obvious explanation was that these abundant, highly charged histones were likely the result of contamination, yet the absence of other histones e.g., H3 and H4, suggested a radical alternative: H2A, H2B, and H2Av are specifically recruited to the surface of LDs in Drosophila embryos, a hypothesis we later confirmed via immunohistochemistry and live imaging. This surprising finding begged the question “how are histones specifically recruited to the LD surface and, most importantly, why?”
A follow up study by our group identified the novel protein Jabba as the anchor necessary to recruit H2A, H2B, and H2Av to LDs2. To investigate potential functions of such recruitment, a previous member of the lab knocked out Jabba and discovered that histones were not only gone from LDs, but that global histone levels were also dramatically reduced. The group hypothesized that histone binding to LDs therefore allows high levels of histone to be stably maintained in the embryo, protected from surveillance mechanisms/degradation, yet made available for packaging during the rapid rounds of DNA replication occurring in early embryos. Indeed, when new histone biosynthesis is impaired, Jabba (i.e. histones on LDs) is necessary for proper development, and in its absence, embryos show phenotypes reminiscent of DNA damage.
During the investigation of Jabba mutants, our group identified an intriguing phenotype suggesting that Jabba/LDs may serve an additional function in histone regulation: in Jabba embryos, the histone variant H2Av over-accumulates in nuclei, while nuclear H2A and H2B are not obviously altered3. This finding provided a paradox: on the one hand, LDs store histones to be used during development; on the other hand, they also prevent histones from entering nuclei. Could LDs serve two distinct roles in histone regulation, storing some histones for use (i.e. H2Av and H2B) while restricting others from being imported into nuclei (i.e. H2Av)? Follow-up studies showed that newly synthesized H2Av can indeed be recruited to LDs in vivo, leading us to propose that LDs act as H2Av buffers, sequestering H2Av synthesized in excess to prevent over-accumulation in nuclei. The mechanism by which buffering is achieved, however, remained unknown.
Our latest study, published last month in eLife, began when we set out to test a fundamental aspect of our histone storage model: if histones are stored on LDs for use during early development, they must then be able to leave LDs and translocate to the nucleus. Using photoactivation, a technique in which we can turn on fluorescent signal within a distinct region to allow for tracking of a particular protein population, we showed that H2Av on LDs can indeed transfer to nearby nuclei in an undisturbed, living embryo. We were particularly struck by one of the results of this experiment, namely by how fast H2Av was lost from LDs: within just minutes, nearly all of the fluorescent H2Av dissipated from the region of initial activation. We hypothesized that such rapid loss from LDs must reflect embryonic demand: in late syncytial blastoderm stages, thousands of nuclei simultaneously undergo replication, creating an immense need for histones that can be supplemented by the supply stored on LDs. To test this notion directly, we quantitated H2Av loss from LDs in earlier stages, when nuclear number and, presumably, histone demand is greatly reduced. To our astonishment, we found H2Av to be lost from LDs with similar dynamics, starkly contrasting our model that loss from LDs reflects demand.
If H2Av is always rapidly lost, despite dramatic changes in nuclear number, where is all of the H2Av going once lost from LDs? To answer this question, we took advantage of a photo-switchable H2Av-Dendra2 that we had generated: this genetic tool would allow us to unambiguously track distinct H2Av populations within the embryo. We discovered that H2Av lost from LDs was not exclusively destined for nuclei after all, but rather re-localized to neighboring LDs. At first, this constant “shuffling” of H2Av between LDs was puzzling, but we then considered whether such behavior may underlie the mechanism of our previously proposed buffering model: H2Av is re-routed back and forth between LDs, thus limiting the free pool in the cytoplasm at any given moment while simultaneously keeping H2Av available for eventual transport to the nucleus.
Based on a number of experimental observations, we developed a formal kinetic model for buffering, incorporating principles of thermodynamics and a few simplifying assumptions; this allowed us to make several key predictions, which we then sought to test experimentally. Using a variety of genetic and microscopic approaches, we were able to demonstrate that LDs are the main regulator of both cytoplasmic and nuclear H2Av. First, we showed that H2Av levels are under limited regulation in the early embryo: manipulating H2Av gene dosage was sufficient to cause a corresponding change in both global and nuclear H2Av levels. This finding was surprising, as the levels of canonical histones are kept constant by elaborate feedback mechanisms despite huge variations in gene copy number4. Second, we altered LD buffering capacity by changing Jabba gene dosage. As predicted, as Jabba levels are increased, nuclear H2Av accumulation is reduced. Third, we used FRAP to show that increased Jabba dosage is sufficient to reduce nuclear import rates of H2Av, in a similar fashion as predicted by our quantitative model.
In early Drosophila embryos, LDs are the main H2Av regulator. H2Av mRNA levels are stable; these represent maternal mRNAs, and there is no zygotic contribution (red dashed line). H2Av synthesized in excess is buffered by LDs, limiting the amount of H2Av available free in the cytoplasm for subsequent nuclear import and deposition onto chromatin.
Limiting H2Av availability via dynamic sequestration to LDs is an elegant way to prevent over-accumulation in the nucleus on short time scales. However, we reasoned that such a mechanism may prove problematic during later stages, when an elongated cell cycle provides ample time for H2Av to enter nuclei (i.e., total nuclear import of H2Av may be too high during long cell cycles, even with buffering). For example, at the time of the mid-blastula transition (MBT), interphase length is dramatically increased (~3x as long as the preceding cell cycle). We asked whether H2Av dynamics were altered during this time and discovered that H2Av becomes statically sequestered to LDs; a transition that occurs within just minutes and is dependent upon the nuclear:cytoplasmic ratio, a well-established molecular “clock” that regulates the timing of MBT events. We speculate that once the rapid cell cycles of the early embryo are finished, it becomes necessary to restrict buffering and allow canonical regulatory mechanisms to take over; investigation into the mechanism of this transition are ongoing and will allow for a direct test of this hypothesis.
To our knowledge, our work over the past several years uncovering the role of LDs in histone regulation provides the most thoroughly characterized example yet supporting a role for LDs in the handling of proteins from various cellular compartments. Furthermore, our work strongly suggests that LDs represent a novel class of histone chaperone and, in the case of the Drosophila embryo, serve as the major regulator of global and nuclear H2Av levels: such a simplified system for histone regulation is remarkable, as most cells employ a variety of mechanisms to control histone levels, including transcriptionally, post-transcriptionally, and post-translationally. In early embryos, the rapid rounds of DNA replication/cell division (~8-15 min per cell cycle) may not allow for canonical regulatory mechanisms to be effective, thus necessitating a simplified means of regulation post-translationally (i.e. buffering): whether buffering exists at other developmental stages remains an open question.
Although we do not yet know if organisms other than Drosophila employ LDs in a similar manner as regulators of histones, histone localization to LDs has been demonstrated in several other organisms/cell types, including mouse oocytes and human cancer cell lines5,6. Now that we have characterized the mechanism by which histones are regulated by LDs, it should be examined whether similar regulation exists for other LD-associated proteins; as LDs are ubiquitous organelles and LD proteomes from many organisms reveal “unusual” proteins, such a regulatory strategy may be widespread. What is clear, however, is that the functions of LDs and their implications for development and cell biology may be far more complex than once thought.
Cermelli S, Guo Y, Gross SP, Welte MA. 2006. The lipid-droplet proteome reveals that droplets are a protein storage depot. Current Biology 16:1783–1795.DOI: https://doi.org/10.1016/j.cub.2006.07.062
Li Z, Thiel K, Thul PJ, Beller M, Ku¨ hnlein RP, Welte MA. 2012. Lipid droplets control the maternal histone supply of Drosophila embryos. Current Biology 22:2104–2113. DOI: https://doi.org/10.1016/j.cub.2012.09.018
Li Z, Johnson MR, Ke Z, Chen L, Welte MA. 2014. Drosophila lipid droplets buffer the H2Av supply to protect early embryonic development. Current Biology 24:1485–1491. DOI: https://doi.org/10.1016/j.cub.2014.05.022
McKay DJ, Klusza S, Penke TJ, Meers MP, Curry KP, McDaniel SL, Malek PY, Cooper SW, Tatomer DC, Lieb JD, Strahl BD, Duronio RJ, Matera AG. 2015. Interrogating the function of metazoan histones using engineered gene clusters. Developmental Cell 32:373–386. DOI: https://doi.org/10.1016/j.devcel.2014.12.025
Kan R, Jin M, Subramanian V, Causey CP, Thompson PR, Coonrod SA. 2012. Potential role for PADI-mediated histone citrullination in preimplantation development. BMC Developmental Biology 12:19. DOI: https://doi. org/10.1186/1471-213X-12-19
Bersuker K, Peterson CWH, To M, Sahl SJ, Savikhin V, Grossman EA, Nomura DK, Olzmann JA. 2018. A proximity labeling strategy provides insights into the composition and dynamics of lipid droplet proteomes. Developmental Cell 44:97–112.DOI: https://doi.org/10.1016/j.devcel.2017.11.020
A postdoctoral position is available in the lab of Helen McNeill at Washington University School of Medicine in St. Louis, Missouri, USA (mcneilllab.wustl.edu). Our laboratory studies how tissue organization and tissue patterning are coordinated in development, using flies, mice and hydra. A major focus of the lab is understanding how Fat cadherins and the Hippo pathway regulate tissue development (Blair & McNeill, Current Opinions in Cell Biology, 2018; Yeung et al., eLife 2017; McNeill & Reginensi, JASN 2017; Reginensi et al., Nat Commun 2016; Reginensi et al., Development 2015; Badouel et al., Development 2015; Bagherie-Lachidan et al., Development 2015; Sing et al, Cell 2014).
We are looking for a highly motivated postdoctoral fellow to join a multidisciplinary research team investigating fundamental problems in development and cell biology. Projects are available in: (1) Using imaging to explore how the Hippo pathway and mechanical feedback impact branching morphogenesis in the mouse kidney (2) Exploring how mutations in Fat4 affect branching and nephron progenitor renewal in mouse models. 3) Using Drosophila as a model to dissect biochemically and genetically Fat signaling in vivo. Assays used include live imaging, RNA-seq, ChIP-seq, mass spectrometry, biochemical approaches and mouse and fly CRISPR mutagenesis.
Applicants should have a PhD and demonstrated relevant research experience. Excellent communication skills and the ability to work in collaboration are essential. A strong background in molecular biology, developmental biology, or cell biology is preferred. Experience in imaging signal transduction, biochemistry and bioinformatics is a plus.
Consistently ranked among the top 10 US medical schools, Washington University School of Medicine offers a highly interactive and stimulating academic environment for scientists in training. The lab is in a highly collaborative environment within the Department of Developmental Biology and Center of Regenerative Medicine. We are located in the heart of the Central West End, a vibrant St. Louis neighborhood adjacent to major cultural institutions and one of the country’s largest urban parks. We offer competitive salary and benefit packages and candidates are eligible to apply for a Rita Levi-Montalcini Postdoctoral Fellowship offered by the Center of Regenerative Medicine.
To apply for this position please submit a CV, a cover letter describing research interests, and contact information for two references who can comment on your research to mcneillh@wustl.edu. Applications will be reviewed promptly until the position is filled. Washington University is an equal opportunity employer and complies with applicable EEO and affirmative action regulations.
Summer of 2018 will genuinely be the summer to remember for all 24 MBL embryology students.
To me, the MBL embryology 2018 course was like a wonderland full of breath-taking experimental adventures, unexpected discoveries, scientific growth and madly passionate researchers. Thus, let me take you on a journey across the five wonders of this course.
1. Woods Hole and the MBL campus.
Woods Hole is a very unique place under our sun. Even though it is tiny and you could see it all in about half an hour, do not be tricked! It has so much to offer! Let’s start with the ocean and all the beaches, including secret beaches (I cannot talk more about this… but if you find yourself there, look for them – you will not be disappointed!)! Stony beach belongs to the MBL campus and is five minutes away from the labs and dormitories. During the day, it always served as a place to slow down, to remind us of how lucky we were to be there and take a very refreshing swimming break between lunch and the afternoon labs. On July nights it had yet another surprise prepared for us – bioluminescence. Swimming surrounded by the bioluminescent unicellular dinoflagellates and embryology course friends under the starry sky felt so magical that sometimes I still wonder if that was just a creation of my tired mind.
Another stunning place, abundant with marine animals, is Eel Pond. Its very photogenic beauty greeted me every morning while walking to get some last-minute coffee and breakfast in Swope building, before our first morning lecture. On the other side of the pond, you can find the Marine Resources Center (MRC), where we got to see a vast variety of marine animals, such as octopuses, skates, sea urchins and many others. After grabbing breakfast, on our way to the Speck auditorium, we passed the Lillie building. This is another special place, and definitely worth visiting. First of all, MBL hosts fantastic Friday evening lectures in the unique Lillie auditorium (recorded lectures can be accessed here: http://videocenter.mbl.edu/videos/). It also has a great library, where we got a chance to hold T. H. Morgan’s Nobel Medal and rare books starting from ‘The Origin of Species’ signed by Charles Darwin himself, to the ‘Opticks: or A Treatise of the Reflexions, Refractions, Inflexions and Colours of Light’ by Isaac Newton and published in 1704.
I want to finish this quick overview of the MBL campus with the Loeb Laboratory Building. This was a building where real wonders happened. This was the place where we spent days and nights familiarising with, studying, observing, grafting, injecting, imaging embryos – from tunicates to nematodes to mammalians… And this brings me to the second wonder of the course.
The after-course cheer together with Shinuo Weng and neural crest field colleagues – Weiyi “Lily” Tang and Andrea Attardi.
2. All the species.
The embryology course lasted six weeks. In the first week, we laid our hands on tunicates – Ciona embryos, and beautiful echinoderms – sea urchin and sea star embryos. We experienced the power of the simple Ciona embryo electroporation method in order to label cells of interest or even acquire transgenic animals. Echinoderm injections were slightly more challenging but were very rewarding once we could observe bright fluorescence under the microscopes. The second week was dedicated to the study of the regenerative capacities of hydra, flatworm planaria and its related species the Hofstenia worm. The things we did to them were mind-boggling… We cut them in half, we chopped them in pieces, and grafted them into each other using a sophisticated method scientifically known as ‘Shish kebab’ technique. We were surprised to see that the animals went on as if nothing had happened, giving us a very much needed relief – we kept them happy and alive. The week continued with indestructible tardigrades and predictable C. elegans worms. On the third and fourth weeks, we jumped onto vertebrate model organisms – chick, mouse, frog and zebrafish embryos. We had the opportunity to perform classical embryology experiments, such as zone of polarising activity (ZPA) grafts into the anterior limb mesenchyme to generate a mirror-image duplication of a developing limb in chick or induce the secondary axis in frog embryos. In week five we continued with developmental biology classics – we got introduced to the icon of developmental genetics that yielded six Nobel prizes in Physiology and Medicine and been awarded to a total of ten scientists, one of whom I had an honour of meeting and having a dinner with during the course – Eric F. Wieschaus. The most important things that I learnt from him about success were – work really hard, never stop being curious, explore in the lab and don’t be afraid of becoming an expert in failing.
In addition to the fruit fly, we got to play with a plethora of different arthropods, such as butterflies and parhyale. This was a transformative week in terms of microscopy imaging skills for all the embryology students. With the wonderful help and valuable tips and tricks of Nipam Patel and a PhD student from D. Sherwood’s lab – Dan Keeley, we finally felt as if we befriended and mastered all the complex and powerful microscopes we had around us. In our final week, we explored the wonders of the ctenophore, cephalopod, gastropod and annelid embryos using our last reserves of energy. It was a great experience to study these non-conventional animal models and try completely new experiments that were never done before with the help of faculty and teaching assistants!
Drosophila embryo stained for even-skipped, fushi tarazzu and DAPI.
3. Knowledge and skills
Every morning we had fantastic lectures by faculty coming from different developmental biology areas. Altogether we covered the most important concepts of development, starting from cytoplasmic determinants and inductive signals required for cellular commitment, to metazoan body plan establishment, all the way to organ morphogenesis and regeneration. Additionally, we looked into evolutionary concepts and questions, new emerging technologies and discussed more philosophical questions, such as the importance of transparent and open science.
Before joining this course, I had a very limited set of embryo manipulations skills. I was mainly used to ‘smash’ zebrafish embryos for the –omics analysis. However, for my future career, I am planning to stay in the developmental biology field and perform more functional embryo experiments. Unmistakably, this course was revolutionary for my developmental biology knowledge and embryo handling skills! At the very start of the embryology course, we had a most important workshop on tool making and handling of marine embryos, led by the tool making virtuoso Jon Henry. At the start, the whole process sounded slightly ‘bonkers’ to me. For example, would you ever consider pulling your eyelashes out and glue them to a glass needle for embryo manipulations? No? Neither had I before this workshop… Nonetheless, we had to make a mouth pipette using rubber tubes, cut our hairs, pull out our eyelashes and eyebrows for gentle embryo handling and dissection tools, very often accompanied by the extensive use of fire to pull and polish pipettes, and tungsten dissection needles… However, soon I understood the power of being creative and do what you can with what you have! Indeed, without all these tools, none of the daring experiments would have been possible. We were also so fortunate to learn from embryo manipulation experts and legends, such as Dave McClay and Ray Keller.
Now that all the embryology students are back to their own benches, I am pretty sure every single one of us is re-making all the tools we learnt and very likely inventing new ones for our own research. (Maybe sometimes while hiding from health and safety officers at night or appearing nuts to our colleagues’ eyes…)
4. Transformative scientific experience
The MBL embryology course is the place where I almost entirely lost the fear of scientific failure. First of all, our course directors, David Sherwood and Richard Schneider, from day one re-assured us that this was not a competitive environment and that we all should be ourselves at all times! This was a great start! Second, we did not have to take any exams or report our progress to anyone! We only presented our work, including failures, in an amusing (a lot of flying balls were involved) and very relaxed manner every two weeks. Importantly, we had a wide range of reagents in our fridges and freezers, top-notch microscopes, experts of the developmental biology field helping us and NO fear! This was the greatest part of the course! To explore, play, try, free our minds from dogmas. And I failed. I failed so badly, so many times. In the beginning, it still gave me somewhat gloomy feelings about not being capable of mastering a technique in a completely new organism in one day (!!!), but after a week or two, these feelings were gone. I was no longer afraid of going for more complicated experiments even though very often I had to embrace the failure. But don’t get me wrong! It is not that from now on I am ready to keep on failing and stay positive about it. No! However, from now on I will no longer be afraid of trying something new, challenging, creative! And I am sure I will fail many more times, but this will not discourage me from pursuing complicated experiments, primarily because in real life I will have more than one or two days to succeed! To sum up, I really share the feeling of one of our great course faculty member, Alejandro Sánchez Alvarado, who, after taking this course himself, knew that he “no longer needed to ask for a permission to do science”.
5. Friendships for life
The cherry on the top of the Embryology 2018 cake was the friendships that formed between the students. Before starting this adventure, most of us were utter strangers to one another. However, on our very first day, we were captivated by each other’s research questions, methodology, talents, and personalities. We were so diverse, and so we had a brilliant opportunity to learn not only from the faculty and teaching assistants but also from each other. The chemistry and dynamics of our group were extraordinary. Every single individual was so hard working, motivated, talented and remarkably friendly and eager to help. We have been through everything together – the lows of failed experiments, the highs of the ones that actually worked, exhaustion, laughter, late nights on the beach, countless hours of conversations in the break room, sharing dorm rooms and so much more that we will never forget. On the 8th of July, our genuine connection symbolically materialised into our victory against the Physiology Course students, during the traditional softball game between the two courses. Overall, I feel very privileged to have attended this prestigious course together with these beautiful people, who are very likely to shape the future of developmental biology field. Spoiler alert – the future of developmental biology is in perfect hands!
Admiring the sunset with my friends Bruno Moretti, Aastha Garde, Sandra Edwards and Andrew Fraser at the Knob, Falmouth, MA.
Lastly, I would like to thank the course directors, all faculty members, course and teaching assistants. You were so great! I would also like to thank all the financial aid contributors that made my attendance possible – Burroughs Wellcome Fund, The Company of Biologists Ltd, Horace W. Stunkard Scholarship Fund, CoB/BSDB Travel Award and the MRC Weatherall Institute of Molecular Medicine Student Travel Fund. Altogether, being part of such a vibrant and brilliant community of developmental biologists made me fall in love with this field once again and reinforced my enthusiasm to continue cracking the remaining mysteries of embryo development!
There is grandeur in this view of life, with its several powers, having been originally breathed a few forms or into one; and that, whilst this planet has gone cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved.
– Charles Darwin
I spent the summer of 2018 at the Marine Biological Laboratory (MBL) in Woods Hole, Massachusetts, US as a student in the Embryology Course. Here, I will reflect on what was a very transformative experience, and while doing so, I would like to share my insights on the beauty and wonder of diversity in developmental biology.
Prior to coming to Woods Hole, my understanding of developmental biology was limited. I studied biochemistry as an undergrad in the Philippines and trained as a chemist. I was not formally exposed to developmental biology research until recently, when I started my PhD in Alexander Aulehla’s Lab at the European Molecular Biology Laboratory (EMBL) in 2016. The desire to broaden my knowledge of underlying principles, mechanisms, and processes in animal development prompted me to attend the Embryology Course this year.
During the Embryology Course, I was introduced to at least a hundred different animal species, spanning both classical and emerging models of development. I worked on organisms beyond what I imagined. I got the chance to learn about and do experiments on several animals like sea squirts and sea urchins, ctenophores and tardigrades, shrimps and snails, and annelids and flatworms. I was fascinated by how the left-right asymmetry of sea squirt embryos significantly relies on its rotation during embryogenesis, and mesmerized by the symmetry and patterning of the skeleton of the pluteus larva of sea urchins. I was enthused by the coordinated beating of cilia on ctenophores, and excited by the unique cleavage pattern of tardigrade embryos. I was astonished by the differences in segmentation in the dorsal and ventral axes of Triops, a freshwater shrimp, and captivated by the establishment of chirality of the shells of snails. I was thrilled by how Pectinaria, a marine annelid, builds its home from grains of sand, and amazed by the regenerative capacity of flatworms like planaria.
ON THE BEAUTY AND WONDER OF DIVERSE EMBRYOS
An illustration of some of the organisms we worked on during the course, arranged to spell EMBRYOLOGY.
We used this for our banner during the July 4th Parade and also printed it on our batch T-shirt.
Illustration by: Ashley Rasys
Integral to studying embryogenesis and animal diversity, the Embryology Course highlighted the strength of comparative embryology in furthering our grasp of unifying principles in development. For instance, the establishment of diverse body plans was a recurring theme throughout the course. It is fascinating how the same toolkit, a set of genes known as Hox genes, lay down the blueprint in patterning the body of very different animals like cephalopods (e.g., octopus) and insects. While all start as single cells, different embryos develop to form very different organisms. The endless beauty and wonder of animals around us, like tardigrades on lichens, ctenophores in sea water, and butterflies on flowers, is intriguing and inspiring. It is even more intriguing and inspiring how some of the developmental concepts and mechanisms could apply not only to animals, but also plants and microorganisms.
In addition to the diversity in organisms that were available to study embryonic development, I had the privilege to interact and do science with a very diverse group of people, coming from different research backgrounds. I learned a lot about regeneration from Jack Allen and Anneke Kakebeen who work on regeneration in planaria and frogs, respectively. Aastha Garde and Sandra Edwards provided insights on cell migration, cell invasion, and epithelial-to-mesenchymal transition. This jived very well with Jayson Smith’s expertise on the cell cycle. On another hand, Katherine Nesbit emphasized the interplay between development of embryos and their environment. Meanwhile, Stefania Gutierrez gave fresh perspectives on animal development with her expertise in colonial tunicates. In parallel, Laurel Yohe and Melvin Bonilla offered a distinct evolutionary point-of-view on acquisition of traits. Andrew Fraser and Shinuo Weng, our mechanical engineers, uniquely saw embryogenesis in terms of forces and mechanics, and Bruno Moretti, our physicist, lended his expertise in optics for functional imaging of developmental processes. Anna Yoney was the go-to person on germ layer patterning, while Darcy Mishkind was the in-house expert on left-right asymmetry. We also had people in the batch who worked on development of reptiles, with Ashley Rasys studying eye development in lizards and Boris Tezak investigating sex determination in turtles. Maximilien Courgeon was most keen on studying the development of the brain and the nervous system. Martyna Lukoseviciute and Marla Tharp were the specialists on gene regulation and chromatin dynamics, while Weiyi (Lily) Tang and Andrea Attardi were the experts on gene regulatory networks. Catherine May was particularly interested in the evolution of cell types, and Shiri Kult was most curious about bone and cartilage development.
While we all worked on the same group of organisms during the course, equipped with our expertise, we tackled the development of these animals at different vantage points. We became more aware of our skill sets, which complemented each other. Being in a diverse group allowed us to challenge dogma, encouraged us to be comfortable with our ignorance, and let us acknowledge the gaps in our knowledge. This created an environment where we embraced naivety, which proved to be conducive in being bold and asking fearless questions. We found ourselves doing classical experiments that were performed by Hilde Mangold and Hans Spemann on frog embryos, Thomas Hunt Morgan on planaria, and Ethel Browne on hydra. We explored the promise of modern approaches in developmental biology research, like advanced and quantitative imaging, 3D printing, and CRISPR-Cas. We took on risky projects, embraced failure (which happened quite often), and celebrated success (when it happened very seldomly). Together with the faculty and the TAs, we relied on each other to supplement our understanding of embryology. Together, we learned beautiful and wonderful things.
ON THE BEAUTY AND WONDER OF DIVERSE RESEARCH BACKGROUNDS
Outdoor Sweat Box (question and answer session) with Susan Strome.
Photo credit: David Sherwood
The enthusiasm, joy, and excitement transcended gender identity and sexual orientation, nationality, and cultural background. This camaraderie went beyond the lab, evident in our Sunday out-of-the-lab trips and spontaneous dance parties, our convergent extension-inspired presentation during the July 4th parade (please see B. Duygu Özpolat’s video here), and our victory during this year’s softball game with the Physiology course. The diversity catalyzed the building of a strong network of scientists and lifelong friends.
The Embryology course also showcased exemplary initiatives to promote inclusive and equitable access to developmental biology research. The microscopes we used, for example, were kindly sponsored by different companies like Zeiss, Nikon, Bruker, and Mizar. During a visit, Manu Prakash, together with Team Foldscope (check out their website here), distributed cheap paper microscopes and highlighted the importance of frugal science. Alexis Camacho-Avila, a very brilliant undergrad from an underrepresented minority group, attended the first two weeks of the course through the Society of Developmental Biology (SDB) Choose Development! Fellowship Program. Moreover, there were generous scholarship grants and fellowships available to cover the expenses of attending the course. Personally, I am grateful for the financial support from the Burroughs Wellcome Fund, the Helmsley Charitable Trust, the Horace W. Stunkard Scholarship Fund, and The Company of Biologists. These initiatives, among others, ensure barriers to diversity in developmental biology research are overcome. Witnessing and experiencing this was empowering.
ON THE BEAUTY AND WONDER OF DIVERSE DEVELOPMENTAL BIOLOGISTS
Embryology Course 2018 class photo, taken at the Waterfront Park in Woods Hole.
Photo credit: Bruno Moretti
Like the embryos we study, the community of developmental biologists has evolved to take endless forms. We are biologists, chemists, and physicists. We dance, ride a skateboard, and win softball games. We are parents, sons, and daughters. We come from different parts of the world, speak different languages, and grow from different cultural backgrounds. While being different, we share the passion to push developmental biology research forward.
Before ending, I would like to use this platform to thank various people who made the Embryology Course special. I thank my classmates whom I shared this truly transformative experience. I thank Christopher Pineda, Amber Rock, and Hannah Rosenblatt, our Course Assistants, who made sure the course ran smoothly. Also, I express many thanks to all the faculty and teaching assistants (TAs), who shared their knowledge and wisdom. I am further thankful to Richard Schneider and David Sherwood, our Course Directors, for granting me this life-changing opportunity. Lastly, I am grateful to my family, my lab, and every one who supported me and encouraged me to apply. I am very grateful to be part of #embryo2018 (a Twitter-friendly collective term referring to Embryology Course 2018 and every one who took part in it).
It has been around a month since I left Woods Hole. While I recollect on everything that happened during the Embryology Course and reflect on how it has a significant impact on what I do now and in the future, the weather here in Heidelberg has become cooler and the leaves on trees have started to turn into different shades of red. This summer is ending most beautifully and most wonderfully.
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