Tuesday, July 30, 2019

[DMANET] PhD Thesis CNRS "From tiling theory to biological fibers"

Dear all,

We have a PhD Thesis supported by the CNRS on the topic "From tiling theory
to biological fibers" directed by Laurent Vuillon at University of Savoie
Mont Blanc (LAMA lab.) and by Claire Lesieur at Lyon (IXXI and ampère


The project investigates the relationships between the geometrical
constraints and the dynamics of a system. The case study is the transition,
induced by an amino acid mutation, of a protein oligomer to a protein
fiber, transition, associated with many diseases (e.g. Alzheimer, type II
diabetes, Parkinson, etc.). To model the fiber, the project is divided in
three steps, each associated with a scale relevant to the problem. First,
the amino acids and interactions affected by the mutation are identified
using a network at the local scale of amino acids. These residues
constitute the new interface required for the fiber. Second, the
interactions between proteins within the interface domain in the fiber are
modeled using a network at the scale of the interface. Finally, the last
scale is the fiber whose construction is modeled using a tiling model. The
combination of both network and tiling models allows reconciling all
experimental data on fiber formation because tiling takes into account a
scale uncovers by networks.

The PhD student will investigate the construction of biological fibers in
general and validate the 3 scale procedure on many real biological fibers.
Thus we are looking for a student trained in mathematics and in particular
in network topology, statistical learning and tiling theory. The student
will consider for example the p53 case whose oligomer has special symmetry,
the ure2p, which combines disordered and structured domains and the
synuclein, which is a disordered protein. In the two last cases, the
network approach will be limited and the student will have to use
information on the fiber properties gathered by the analysis of the fiber
database combined with experimental data on the fiber to investigate the
scale 3 as a first step. Thus the network approach will come after the
global fiber scale, and it will be based more on experimental data of amino
acid contacts and basic geometrical constraints from 2D and 3D interactions
in proteins. The sequences of the proteins will be investigated in terms of
first neighbors to try to design a network of interactions that respond to
some mathematical invariant properties based on our database of amino acid
neighborhoods. This will be a challenging task but will completely
generalize the procedure to any case.

Best regards
Laurent Vuillon

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