From fly connectomics to molecular and cellular mechanisms of cytoplasmic dynein, from genetic code fidelity to the molecular mechanism of trans-translation – the Max Perutz Student Prizes were awarded to a diverse range of PhD research
Alex Bates’ work focused on integrating various data – physiological, behavioural and neuroanatomical – to understand the circuit basis of olfactory behaviour in the vinegar fly, Drosophila melanogaster. For example, how learned and innate olfactory circuits cooperate to enable memory recall.
Alex from Greg Jefferis’ Group identified neurons that might be involved in generating instinctive behaviours and built a map of neuronal connectivity between these cells, a ‘connectome’. This map can be used to predict how information might be routed through important parts of the fly brain. “Doing so helped us understand which connections are important for generating certain behaviours, for example attraction to food-odours, or the fly’s ability to recall bad memories about smells,” Alex said. Going forward, he wants to continue investigating the fly brain. “There is a lot we don’t know about this small animal, and we can use it to ask questions that we have no hope of answering in larger animals,” added Alex. “I have received a lot of strong support from my supervisor, Greg, and the other Jefferis lab members throughout my time at the LMB. The relationship between you and your lab mates is key to having a happy and successful PhD.”
Helen Foster of Andrew Carter’s Group was recognised for her work on the molecular and cellular mechanisms of cytoplasmic dynein, a motor protein moving on microtubules. Helen contributed crucial insights and experiments to the work that unravelled the activation and inhibition mechanisms of dynein that depend on binding of dynactin and a cargo adaptor. Her work on the in situ structure of dynein as it transports vesicle cargos along neuronal axons is daring and provides a unique platform for our understanding of dynein-mediated cargo transport in cells.
Helen’s research is unique and therefore, no one in her lab had ever used the methods before. “I had to learn a huge number of new techniques during my PhD, and I did that with the help of people all across the LMB. I ended up working in nearly every department and don’t think this kind of collaborative work could have been done anywhere else,” said Helen.
Ross Hill of Gerry Crossan’s Group discovered that the DNA repair factor ERCC1 is required during epigenetic reprogramming and expansion of primordial germ cells. In his study, Ross showed that germ cells that fail to undergo DNA cross-link repair accumulate DNA damage, and are efficiently and specifically deleted. This partly explains how fidelity of the genetic code is maintained between generations.
And like most PhDs, Ross’ also had its fair share of challenges. One of his primary challenges was that primordial germ cells, which require DNA crosslink repair, are very rare and found deep within developing embryos. This made any detailed analysis much more complicated. “Fortunately, the LMB is equipped with excellent light microscopy facilities that allowed us to interrogate the development of these rare cells. Also, with the help of the Flow Cytometry facility we were able to isolate primordial germ cells from embryos and perform more detailed molecular analyses,” said Ross. He added that he is grateful to the skilled staff of the LMB that made this possible.
Chris Rae of Venki Ramakrishnan’s Group was awarded for his work on the molecular mechanism of trans-translation, a rescue pathway that allows bacterial ribosomes to escape a stall when they encounter the premature ends of messenger RNA. Careful and imaginative experimental trapping of reaction intermediates allowed Chris to visualise by cryo-EM key steps in the reaction that involves transfer-messenger RNA (bacterial RNA molecule with dual tRNA-like and messenger RNA-like properties) but also a number of canonical and non-canonical protein factors, whose actions are now understood in great detail.
As is the case in many structural biology projects, reaching high enough resolution to answer the interesting questions was a significant effort. Chris said, “The community of electron microscopists and the support of the core facility made it possible to collect and process the large amount of data required. In the future, I’m hoping to do a postdoc where I can use cryo-EM to explore the mechanisms of other large macromolecular complexes.”
The Perutz Student Prize, awarded by the Max Perutz Fund (UK charity 1129597), is an annual award for outstanding PhD work done at the LMB. Nominees should normally hold, or have recently held, a studentship at the LMB, and have spent less than four years on their PhD. The Fund was established for the promotion and advancement of education and research in molecular biology and allied biomedical sciences. The fund also gives out awards for student travel and postdoctoral fellowships.
The fund was set up in June 1980 in honour of the LMB’s founder, Max Perutz.