The BSDB had its joint Spring Meeting with the BSCB earlier this year in April (10th -13th). It was my first time at the Meeting, which had been enthusiastically sold to me as “a good one, a fun one – they have a pub quiz!” and although I had been ‘sent to Coventry’, I have to confess, I had a great time. It was a busy 3 days, brimming over with interesting talks and stellar plenary and medal lectures. The concurrent sessions were on topics of interest for both cell and developmental biologists and so I ended up flitting between the talks of the concurrent sessions each day. Unfortunately, due to the impossibility of being in two places at once, there were excellent talks that I did miss and I apologise to these speakers for my non-attendance. I also want to say a big thank you to the speakers who have very kindly given me permission to write about the unpublished work they presented.
The meeting started, for me, with a Career Workshop on the Sunday afternoon. It was organised as a series of roundtable discussions with lecturers, group leaders, and people in industry, science publishing and communication. I got to speak to Paul Conduit, a Henry Dale Fellow at the University of Cambridge, Anne Wiblin from Abcam who provided the perspective of science life in industry, and Catarina Vicente from the Node, with whom I discussed the power of Twitter (and cakes) for communicating science.
Sunday evening’s plenary lectures were given by stalwarts – Mark Kirschner gave the BSDB Plenary Lecture and Ruth Lehmann the BSCB Plenary Lecture.
Mark Kirschner’s lecture sought to give quantitative answers to a fundamental question – “what is the economy of RNA and protein in embryonic development?’ with impressive technology and precision. By examining the dynamics of RNA and proteins on a single cell level, the Kirschner group has been able to show that while the correlation between the mRNA and protein levels is 0, the protein synthesis rate correlates with the mRNA synthesis and decay rates (Peshkin et al. 2015).
Jordan Raff, while introducing Ruth Lehmann, mentioned that he remembered her work, where injecting nanos mRNA into the anterior of the embryo caused the formation of an embryo with “essentially 2 bums”. Co-incidentally Ruth Lehmann came back to the “2 bums” embryo in her talk in the context of mitochondrial segregation in primordial germ cells. A second research story she presented was of mitochondrial maturation during germline cyst formation – developmentally regulated folding of the inner mitochondrial membrane into cristae is dependent on ATP-synthase dimer formation (Teixeira et al. 2015).
In a break with tradition, the student and post-doc social did not have a pub quiz, but instead we were put into random pairs and teams to build spaghetti towers and play science Pictionary. It was an excellent way to meet fellow attendees and bond over our total lack of talent at either drawing or building design (or complete mastery of, in a few cases).
Monday was a day packed with scientific goodness – 4 sessions of talks, 2 medal lectures and 2 poster sessions! The sessions of the morning were Cell and Tissue Architecture and Evolution. In the Cell and Tissue Architecture session I listened to Val Wilson talk about neuromesodermal progenitors (NMPs) – bi-fated cells at the caudal end of the mouse embryo who contribute either to the spinal cord or paraxial mesoderm, depending on their position in the progenitor region. She talked about NMP behaviour during the formation of the mid-trunk (Wymeersch et al. 2016). Olivier Hamant went on to talk about the role mechanical forces play in providing growth cues – microtubule dynamics in response to stress give the characteristic shape of sepals in Arabidopsis (Hervieux et al. 2016). Yara Sanchez Corrales showed how tube morphogenesis in the embryonic Drosophila salivary gland occurs. Cell division does not occur during the process and tube formation is driven entirely by cell shape changes and rearrangements. Their live cell imaging approach allows for the cell shape dynamics to be analysed in 3D.
In the Evolution session, I took in the talks of Marie-Ann Felix, Andrew Gillis and Marty Cohn. Marie-Ann Felix presented work aimed at understanding the effect of random mutation at the phenotypic level. They assayed the sensitivity of the vulval precursor cells of C. elegans to fate changes after the accumulation of random mutation and find that the P3.p vulval cell fate is most affected and is sensitive to mutations in many loci. This means that mutational effects can produce altered responsiveness to signalling pathways and, in this view, the P3.p cell fate is evolving the fastest. Andrew Gillis showed that Sonic hedgehog is required for gill arch anteroposterior polarity and for the branchial ray development in the gills of sharks, skates and rays (Chondrichthyans). This finding parallels paired fin development, giving traction to the hypothesis that there is serial homology between paired fins (and tetrapod limbs) and Chondrichthyan gill arches. Marty Cohn talked of the origin of cartilage – while true cartilage is considered to be unique to vertebrates, invertebrates like cuttlefish show cartilage-like tissue that develops via a deeply conserved gene regulatory network (Tarazona et al. 2016).
The afternoon sessions were Hijacking Cell and Developmental Processes and Polarity. In the Hijacking session, Shuchen Zhang presented her work trying to understand the genetic interactions of Sox2 that underpin its dual functions as a regulator of pluripotency in human embryonic stem cells and as a key factor in neural differentiation. Steve Jackson presented work on how cell-based screens in his lab have identified novel drug targets for cancer therapies, focussing on a PARP inhibitor that is now used in chemotherapy to treat hereditary ovarian cancers. In the Polarity session, Takashi Hiiragi showed that the apical domain of cells is instructive for the initial symmetry breaking in early mouse embryonic development by some fantastic live imaging. Nate Goehring showed us how through the use of novel small molecules, his lab has manipulated the activity and localisation of kinase PKC to understand the PAR polarity network in the C. elegans embryo. Ray Keller talked of the “mechanome” and the game plans – convergent extension, epithelial to mesenchymal transition and convergent thickening (driven by changes in cell affinity) – that tissues use to generate the forces required to drive morphogenesis in amphibians (Pfister et al. 2016).
The evening was host to BSCB’s Hooke Medal and BSDB’s Waddington Medal lectures. Tom Surrey was the recipient of this year’s Hooke Medal. He presented 3 facets of his lab’s research into understanding microtubule dynamics. Through impressive time-lapse fluorescence microscopy movies, we were shown the dynamics of microtubule growth, catastrophe (Duellberg et al. 2016) and nucleation (Roostalu et al. 2015) in in vitro reconstitutions. Tom Surrey’s medal lecture (and all other medal lectures of the meeting) can be watched here:
The recipient of the Waddington Medal was completely shrouded in secrecy until just minutes before the lecture, Ottoline Leyser (the BSDB president) even engaging the audience in a little guessing game to introduce him. It was Enrico Coen! He started his talk with a series of sketches of bulls by Picasso and posed the question – what is harder, describing something with every detail or capturing its essence? In a very cinematic presentation with beautiful images and movies, videos of collaborations with potter and glass-blower friends set to a lush soundtrack and a live demo of growth conflicts with melting plastic, Enrico Coen gave us the essence of his obsession – the snapdragon flower. The talk strongly resonated with the conference. References were made to it in almost every subsequent session and he might just have convinced everyone to drop everything they are doing and start studying snapdragons and bladderworts. I have it on good authority that he believes a good talk is like the movie High Noon. I know what you’ll be doing at your next lab meeting…
On Tuesday morning I attended the Growth and Cell division session. I heard Anja Geitmann talk about the mechanisms the pollen tube uses to grow towards the ovaries in plants and it genuinely seems a bit of a wrecking ball. Using a microfluidic device her group has been able to measure the pressure the pollen tube can exert – it is about 150kPa. That’s the pressure in a car tyre! Shane Herbert presented data showing that asymmetric cell divisions and Notch-Delta mediated lateral inhibition establishes the hierarchy of motility in the endothelial tip cells that allows for the leader-follower mode of cell migration in angiogenesis and Silvia Santos brought the session to a close by shedding some light on the temporal control of the cell cycle. Mitosis time is typically short and constant and insulated from the timing of early cell cycle phases. This seems to be regulated by the positive feedback of Cdk phosphorylation. Breaking the feedback leads to longer, more variable mitosis that is coupled to the interphase time.
The Graduate Student Symposium was held on Tuesday afternoon. Despite being fraught with technical difficulties, it was one of the most enjoyable and engaging sessions of the meeting. Kudos to the speakers for their quick thinking and improvisation in face of the ‘your-presentation-won’t-play’ challenge! We heard about (and saw, when the computers co-operated) Mycobacterium infection, cell divisions in motile cells and stretched tissues, centrosome clustering in cancers, neuroretinal self-organising aggregates, neural tube lumen formation, neuromesodermal progenitors, segmentation in spiders and flies, zebrafish cilia formation and calcium signalling in angiogenesis.
Uri Alon provided a brief and unexpected (i.e. not in the schedule) interlude titled the ‘The Life Scientific’ before the Woman in Science Medal talk. With a flip chart, a guitar, witty and tuneful songs that required back up singing by the audience, Uri Alon highlighted the need to acknowledge and discuss the emotional and subjective nature of the scientific process. Feeling lost, stuck and being in “the cloud” is all part of doing innovative science. Please, please watch his TED talk on YouTube, whether you are lost in “the cloud” or not. It is Game of Thrones-level essential viewing.
The Woman in Science Medal was awarded to Lidia Vasilieva for her work in understanding mechanisms of gene expression. Lidia began by highlighting the progress made in science to help women achieve their goals and then focussed on her work in understanding the regulation of gene expression. Her lab has discovered that exosome mediated RNA degradation, in co-operation with the splicing machinery, can regulate levels of mRNA (Kilchert 2015).
Abigail Tucker was the recipient of the first Cheryll Tickle medal. The Cheryll Tickle medal is being awarded by the BSDB to a mid-career female scientist for outstanding contributions to her field. And Cheryll Tickle herself was present to award the medal to Abigail Tucker. She quipped that she was rather glad that the BSDB went with her full name for the medal as “the Tickle medal” might suggest an award for something else (but the medal does feature a feather (!)). Abigail Tucker’s talk was a simultaneous career and life retrospective. She presented a career timeline, talking briefly about her PhD and postdoc work before taking us through the current activities of her lab studying the development of opossums, pit vipers and cobras. I imagine that this is the kind of work Indiana Jones would do, if he were a scientist. She also highlighted personal events of great significance on her career timeline. It is both inspiring and heartening to know that it is possible to have a thriving scientific career alongside a family.
Wednesday morning was a bit of tough start thanks to the late-night/early-morning revelry and dance floor antics that followed the conference dinner. But, I did manage to make it for Wendy Bickmore’s opener for the information processing session at 9.30am (!) about enhancer-promoter interactions studied by chromatin conformation capture and single molecule FISH. She was followed by Stefano De Renzis who showed how he can reconstitute invagination in embryonic Drosophila tissues that normally wouldn’t by optogenetically modulating the local actomyosin contractility.
I then caught the last 2 talks of the ageing and regeneration session. Yves Barral showed us how the bud lineage in budding yeast stays immortal – a diffusion barrier made of phytoceramides separates the mother and daughter preventing exchanging of membrane proteins and allows age to accumulate in the mother cell. Allison Bardin talked about mechanisms causing instability of the genome in adult stem Drosophila intestinal stem cells and how this affects homeostasis. Using an X-linked Gal80 construct she showed that mitotic recombination promotes loss of heterozygosity. She also showed that genomic rearrangements in these cells could lead to the spontaneous development of neoplasias in male flies (Siudeja et al. 2015).
Elena Scarpa, recipient of the Beddington medal for the best PhD thesis, presented her work in Roberto Mayor’s lab before Uri Alon brought the conference to a close. Elena showed the role of cadherins and the interplay of intracellular and external forces in contact inhibition of locomotion in migrating neural crest cells (Scarpa et al. 2015). Uri Alon spoke about how quantitative thinking could be brought into discussions of morphology and showed work from his lab where phenotypes had been studied using Pareto optimality. The approach is based on the logic that no phenotype can be good at all tasks and there is a trade-off with respect to the tasks to ensure maximal fitness, leading to optimal phenotypes. These phenotypes fall into simple shapes such as lines and triangles (Pareto fronts), the vertices representing an archetype – phenotypes that are specialised at a single task (Hart et al. 2015).
To sum up my experience at Warwick – I had spent 3 days being inspired by great talks, fascinated by all the new science I had heard, making new friends, having interesting discussions about my project and science in general. I discovered I am as hopeless at art as I am at origami and have no future at all as an architect. I was also strangely buoyed by the knowledge that most of my experiments are destined to fail. I returned home and fell into the dreamless slumber of a happy and exhausted child and woke up refreshed and ready to get lost in “the cloud”.