At the end of a highly stimulating LMB Lab Symposium, Jan Löwe, LMB Director and Chair of the Max Perutz Fund (UK charity 1129597), was delighted to announce the winners of the Max Perutz Student Prize and the newly awarded Brenner Postdoc Prize.
The Max Perutz Student Prize has been awarded annually since 1984 for outstanding PhD work performed at the LMB. Nominees normally hold, or have recently held, a studentship at the LMB, have spent less than four years on their PhD and their prize-winning work should be published. The 2018 prize has been jointly awarded to three students from across the LMB.
Szymon Juszkiewicz from the Cell Biology Division has been working with Manu Hegde on how cells detect excessively slow ribosomes. Szymon showed that ribosomes become ubiquitinated when stalled and identified the ligase. In a second piece of work, he also showed, in collaboration with Venki Ramakrishnan’s group, how the ubiquitin ligase, ZNF598, detects the collision of two ribosomes, forming a di-ribosome complex.
Christina Gladkova from the PNAC Division has spent her PhD with David Komander studying the activation of parkin, an E3 ubiquitin ligase that works on the surface of mitochondria, marking them for removal. After being involved in the discovery of phospho-ubiquitin and its new conformational switch, Christina deciphered the molecular mechanism of parkin activation by phospho-ubiquitin, that parkin phosphorylation is important and also showed the conserved nature of the mechanism.
Max Wilkinson from Kiyoshi Nagai’s group in the Structural Studies Division has solved a very important cryo-EM structure of the spliceosome, the complex that facilitates the removal of introns from mRNA before translation into proteins. The structure of the ‘P complex’ showed, for the first time, how splice site selection works with only a very small number of conserved nucleotides near those sites, solving a long-standing mystery at the heart of the central dogma of molecular biology.
The Brenner Postdoc Prize is being sponsored by Royalty Pharma through the Max Perutz Fund. The Prize will be presented annually to outstanding LMB postdocs who have been in post for less than six years. This year’s inaugural prize has been awarded to 5 exceptional scientists.
Benjamin Falcon from the Neurobiology Division has been working with Michel Goedert and Sjors Scheres on structures of amyloid fibres formed by the microtubule-stabilising protein tau. Ben’s work shows that tau filaments isolated from brains of dementia patients with two different diseases, Alzheimer’s and Pick’s, form different filament structures. The work reinforces the idea that tau filaments are directly involved in disease progression and may lead to a much better understanding of the origins of tau amyloid fibre formation.
Simonas Masiulis, from Radu Aricescu’s group in Neurobiology, has solved cryo-EM structures of GABAA receptors, major mediators of inhibitory neurotransmission in the mammalian central nervous system. The work directly demonstrates how the receptor functions depending on GABA (γ-aminobutyric acid) binding and also how some widely-used general anaesthetics and benzodiazepines (e.g. valium) modulate the receptor’s activity.
Juan Garaycoechea from the PNAC Division has been working with KJ Patel on the preservation of blood stem cells against toxic products of metabolism. Fanconi anaemia (FA) occurs because the repair function that removes aldehyde-induced DNA crosslinks is dysfunctional. Published in two separate studies, Juan showed which cells within the bone marrow are lost in the absence of DNA repair when crosslinking occurs. He also showed that normal metabolism produces enough damaging aldehyde for the disease to progress, in the absence of externally applied alcohol that is metabolised to aldehyde.
Claudio Alfieri, from David Barford’s group in the Structural Studies Division provided cryo-EM snapshots of key mitotic regulation events. In two separate but connected studies, Claudio demonstrated in detail how the spindle assembly checkpoint functions through the inhibition of APC/C by the mitotic checkpoint complex MCC and how in turn MCC inhibition of APC/C is released through the AAA ATPase TRIP13.
Ana Casañal from the Structural Studies Division has been working with Lori Passmore on mechanistic insights into eukaryotic 3′-end processing. The work overcame many hurdles and provided the first view of the polymerase module of cleavage and polyadenylation factor (CPF) that adds poly(A) tails to mRNAs, one of the key features of eukaryotic gene expression.
The Max Perutz Fund was set up in June 1980 in honour of the LMB’s founder, Max Perutz, and was established for the promotion and advancement of education and research in molecular biology and allied biomedical sciences.