ISMB Commentary: An unexpected role for the enzyme Glutamine Synthetase

October 2018

Prof Francesco Gervasio’s group has contributed to the discovery and clarification of an unexpected, yet fundamental, role of the enzyme glutamine synthetase.

Glutamine synthetase (GS) is an enzyme that converts glutamate and ammonia to glutamine.  GS is expressed in endothelial cells, fundamentally regulating vascular development. However, a group of scientists led by Prof Peter Carmeliet at VIB in Belgium together with Prof Francesco L. Gervasio found that it surprisingly shows little glutamine synthetizing activity in these cells. Instead, GS localizes in membranes due to an expected (and so-far, unknown) auto-palmitoylation activity. This moonlighting activity turns out to be fundamental for vessel sprouting. However, it was unclear how it happens and which residues are involved. The state-of-the art models and simulations by Prof. Gervasio’s group were able to solve the mystery, showing how palmitoyl-COA binds to the active site (see figure, left) and reacts with cysteine 209 to form a covalent bond. Site-directed mutagenesis of Cys209 later confirmed the computational prediction and validated the proposed mode of action. This new finding, published by Nature at the beginning of September, has important implications for anti-cancer drug discovery, as it might lead to new drugs blocking the vascular development in solid cancers.


Role of glutamine synthetase in angiogenesis beyond glutamine synthesis
Eelen, G.,…, Gervasio, F.L.,…, Carmeliet, P.
Nature (2018) 561, 63-69

Posted by ubcg49z in Commentaries, News, Publications

Film: ‘The Virtual Human’

October 2018

A collaboration between the ISMB's Prof Peter Coveney and Prof Andrea Townsend-Nicholson with Prof Blanca Rodriguez at University of Oxford, Prof Marco Viceconti at University of Sheffield and Prof Alfons Hoekstra at University of Amsterdam, 'The Virtual Human' is a film describing the recreation of a human being in silico, including IMAX video composited on the Marenostrum supercomputer. It was produced by Barcelona Supercomputing Centre and CompBioMed H2020 Centre of Excellence in Computational Biomedicine, led by UCL.

The film has been screened at the IMAX cinema as part Science Museum lates and at the 2018 Cheltenham Science Festival.


Barcelona Supercomputing Centre

Posted by ubcg49z in Achievements, News

Professor Andres Ramos receives new MRC programme grant

July 2018

Congratulations to Professor Andres Ramos on being awarded an MRC Programme grant for the project: ‘Molecular mechanisms regulating mRNA transport and local translation in neurons‘.

The research will investigate the crucial role played by RNA binding proteins in the regulation of the transport and translation of mRNAs in dendritic and axonal locations. The regulation of mRNA translation in space and time creates distinct local biochemical environments in the cell, which are essential in mediating inter-neuronal communication and establishing neuronal networks.

This MRC programme is a collaboration between groups at ISMB, the UCL Sainsbury Wellcome Centre, the Francis Crick Institute, the UCL Institute of Neurology and the Albert Einstein College of Medicine in New York. The grant will run from 2018 to 2023.

Posted by ubcg49z in Grants awarded, News