Field: Life Sciences & Biomedicine
Host: University of Edinburgh
Funder: Medical Research Scotland
Fellowship Title: Computational approaches to understand the effect of stepwise glutamate binding on AMPARs’ conductance
Dr Sergio Menendez obtained a BSc degree in biochemistry and a PhD in molecular oncology (University of Dundee, 2005), followed by various postdoctoral Research Fellow positions working at the interface between molecular oncology and stem cell biology. After a career break for family reasons Sergio is resuming his research career with the help of a Daphne Jackson Fellowship funded by Medical Research Scotland. He is interested in working towards bridging the gap between molecular and mathematical modelling methodologies in neuroscience. The Daphne Jackson Fellowship offers him an excellent opportunity to gain a new skill set working at the interface of molecular biochemistry, mathematical modelling and neuroscience, while taking advantage of his experience in cellular and molecular biology.
His project will study the mechanisms underlying the transmission of signals mediated by glutamate at the synaptic connections between neurons, both in health and disease. Glutamate released from presynaptic neurons first activates postsynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-receptors (AMPARs), which are integral membrane ion channels that allow cations to flow into the receiving neuron upon opening. This causes a change in membrane potential of the postsynaptic neuron, triggering a cascade of events responsible for the propagation of the excitatory signal. He will use a computational model, based on state-of-the-art single-channel molecular dynamic simulations and computational electrophysiology to study how glutamate controls this process and triggers the activation of individual AMPARs’ subunits upon binding. This will enable him to characterise individual steps in AMPAR activation and elucidate their effect on conductance. He will perform experiments both in wild-type and disease-causing mutated receptors, in the hope of uncovering novel mechanistic insights that could eventually lead to therapeutic interventions.
In his spare time Sergio loves getting out into the beautiful Scottish hills, whether summer or winter, in pursuit of any outdoor activity that will keep him warm.
