2017 witnessed the departure of two of our group leaders. Matthieu Louis, a junior group leader, moved to the University of California at Santa Barbara, and James Sharpe, a senior group leader, became the first director of EMBL Barcelona. During their time at the CRG, Matthieu’s lab completed an absolute tour de force of technology development to establish the Drosophila larva as a premier system in which to quantitatively study sensory perception and animal behaviour. The lab discovered new behaviours, developed methods to study them, elucidated the wiring diagram of the larva olfactory system, studied its evolution, and, through the use of a closed-loop optogenetic tracker, developed and tested a multi-level model for how the animal integrates dynamic olfactory signals.
James’ lab has been part of the program since it started in 2006 and James was coordinator of the program from 2011 to 2017 and so contributed enormously to the culture of the program and the style of the science we do. The lab’s major achievement whilst at CRG was the demonstration that the mechanism that specifies mammalian digits is a molecular Turing system. A vast amount of technology development underlies this major achievement, and the lab continued to develop microscopes and modelling approaches throughout its time at CRG. They also published a fascinating body of work exploring the design space of dynamic gene networks, and, in collaboration with a former program member, Mark Isalan, built some of these patterning networks in bacteria. We may have five digits, but it turns out there are six mechanisms for three genes to interpret a morphogen gradient to build a stripe! We are very excited that James will direct the new site EMBL Barcelona. The institute will focus on the biology of tissues and organs and will bring an additional 6-7 systems biology labs to the PRBB, giving the building an unrivalled concentration of quantitative and integrative biology labs in Europe.
We are very proud of the achievements of both Matthieu’s and James’ labs – theirs is exactly the kind of original, ambitious, difficult, and long-term quantitative science that we aim to develop in the program. We wish them luck in their new homes and expect to hear great things coming out of their labs for many years to come. We will miss their scientific vision, friendship, and support.
2017 has been quite a productive year for the program. Ben Lehner’s lab published their discovery of a long-lasting and chromatin-associated transgenerational epigenetic memory of the environment in C. elegans, as well as their discovery that maternal age is a major influence on phenotypic variation in this species. These two studies continue the lab’s long-running interest in understanding the causes of phenotypic variation amongst genetically identical individuals. The lab also showed that the signatures of clustered mutations in >1,000 human tumours can be used to identify the molecular mechanisms that cause mutations, including the discovery of a new mutation process that targets mutations to active genes in tumours associated with carcinogen exposure, including alcohol consumption. Luis Serrano’s lab continued to develop Mycoplasma pneumonia as a ‘therapeutic chassis’. They also published the structure of the Mycoplasma chromosome at 10 kb resolution and used random mutagenesis and deep-sequencing to determine key sequences of promoter and untranslated regions that influence transcription and translation efficiency in this bacterium. Mara Dierssen’s lab continued their work on understanding the changes in neuronal architecture and connectivity that disrupt cortical and hippocampal function in genetic cognitive disorders. They also showed that Neurotrophin-3 infusion rescues fear extinction impairment in a mouse model of pathological fear. Manuel Irimia’s lab published the most comprehensive database of alternative splicing events released to date. They also elucidated the role and evolution of Esrp-dependent splicing programs in morphogenesis. In addition, by molecularly characterising the development of the amphioxus neural tube, they presented an important new model for vertebrate brain organization and evolution.
In recognition of their achievements, Manu Irimia was elected as an EMBO Young Investigator, Ben Lehner was elected as an EMBO Member, and Mara Dierssen received both the BigVang Medal and the Trifermed Social Impact of Healthcare Award.
Finally, Nick Stroustrup joined the program as a junior group leader. Nick’s Dynamics of Living Systems Lab will develop experimental and computational methods to characterize where, when, and why aging occurs, and how we might effectively intervene in its progression. Whilst at Harvard, Nick developed the ‘Lifespan Machine’, which allows researchers to track tens of thousands of nematodes throughout their entire lifespan and he used this to discover a universal scaling law for how interventions alter lifespan. Nick continues the program traditions of hosting groups with an engineering-driven approach and groups tackling a well-established question from a very original (orthogonal) angle. Welcome Nick!