Cutting-edge science for health

Computational analysis of surface mobility of NMDA receptors in hippocampal synapses

Laboratory of Computational Neuroscience

PhD project: Computational analysis of surface mobility of NMDA receptors in hippocampal synapses

In recent years, it has become clear that the structure of neuronal synapses is highly dynamical, with many of the molecular constituents turning over at a time scale of minutes. This fast trafficking of molecular components into and out of synapses has important functional consequences. In mammalian excitatory synapses, the surface mobility of AMPA and NMDA receptors was shown to play key roles in synaptic plasticity and in Hebbian learning. Current fluorescence microscopy techniques permit to track the motion of single receptor molecules over extended periods, and thus probe the dynamical organization of the synaptic membrane.

The goal of the PhD project is to carry out a detailed quantitative analysis of the surface mobility of NMDA receptors tagged with Quantum Dots. The receptor trajectories, recorded in hippocampal neuronal cultures under a variety of experimental conditions, will be analyzed using computational methodologies from biophysics and statistical physics. Mathematical modeling of the receptor population trafficking will be implemented in order to analyze functional consequences of variations in surface mobility. The project will be carried out in close collaboration with the laboratory of dr. Martin Horak in the neighboring Institute of Experimental Medicine CAS. While the primary focus of the PhD project will be on computational analysis and modeling, opportunities to participate in the experiments and data collection will be available.

Candidate’s profile (requirements):

We are seeking outstanding candidates with Master's degree or equivalent in physics, applied mathematics, bioengineering or related fields, or those expecting to obtain this degree by July 2020. The candidates should be fluent in English and have strong communication skills. Previous experience with computational projects is an advantage. Flexibility and ability to learn in an interdisciplinary environment are essential.

Supervisor: Martin Zapotocky,  Ph.D.  

Relevant publications:

Skrenkova H, et al., N-glycosylation regulates the trafficking and surface mobility of GluN3A-containing NMDA receptors. Front. Molec. Neurosc. 11, art.188 (2018).
Vyklicky V, et al., Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule. Sci.  Rep. 5, art. 10935 (2015).