Dr. Marie Doumic, INRIA Rocquencourt, BANG project team, France
Wednesday 10th December, 4.00 p.m., Stacey Lecture Theatre 1
Amyloid diseases are of increasing concern in our aging society. They are a group of diseases which involve the aggregation and the deposition of misfolded proteins, called amyloid, which are specific for each disease (PrP for Prion, Abeta for Alzheimer’s). In a healthy state, they remain monomeric, but when misfolded they propagate the abnormal configuration and aggregate to others, forming very long polymers also called fibrils. Elucidating the intrinsic mechanisms of these chain reactions, most probably specific for each disease, is a major challenge of molecular biology: do polymers break or do they coalesce? Do some specific sizes polymerize faster? What is the size of the so-called nucleus, i.e. the minimum stable size for polymers? Does polymerization occur by monomer, dimer, or i-mer addition? On which part of the reactions should a treatment focus to arrest the disease? Up to now, only very partial and partially justified answers have been provided. This is mainly due to the extremely high complexity of the considered processes, which may possibly involve an infinite number of species and reactions (and thus, an infinite system of equations). Mathematical modelling, simulation and parameter estimation methods are thus required and already proved to have a major impact on understanding amyloids’ kinetics. In this talk I will review existing results and explain our approach, which is based on combined ODE-PDE (and more recently stochastic) models. I will also develop some of our recent findings, both in a mathematical and more general side, with some focus on specific applications for different proteins.