Physics Friday Colloquia
Friday colloquia Autumn 2016
This colloquium will be at a slightly unusual time and place:
Time and place: 12:15 in the lunch room D5-175
Prions and amyloids: self-replicating protein pathogens
Recently the prion disease Chronic Wasting Disease was unexpectedly discovered in Norway in reindeer and moose.
Prion diseases are lethal, infectious diseases associated with prion protein (PrP) misfolding. A large number of mammals are susceptible to both sporadic and acquired prion diseases. Prion diseases diseases are infectious. Transmissibility of prions occur through seeded conversion of endogenous normal PrP to misfolded PrP. The process is reminescent of the progression of amyloidosis of which 30 proteins are linked in diverse diseases.
Transmissibility is surprisingly efficient in prion diseases and given the rapid disease progression following initial symptoms the prionoses stand out from other amyloidoses. Several amyloidoses likewise appear to be transmissible under certain circumstances, especially in experimental settings, but with a much slower disease course. In vitro the prion replication process can be mimicked using synthetic PrP. Seeded conversion of various PrP sequences display significantly decreased lag phases demonstrating that nucleation dependent polymerization is a dominating mechanism in the fibrillation process. Different conformational states of PrP within prions appear to dictate the disease phenotype. A major question is what makes a certain prion transmissible and what makes it neurotoxic?
Polyelectrolytes - The Minefield
Flexible polyelectrolytes can be described as highly charged polymers. It is therefore tempting to reuse the the concepts and theories that have successfully described neutral polymers and just add electrostatic interactions. However, the long-ranged nature of the electrostatic interactions and the presence of counterions break some of the underlying assumptions. Electrostatic persistence length and osmotic pressure are two areas where uncritical application of "common knowledge" has led to both unnecessary controversy and false consensus. Becoming aware of these pitfalls is the first step towards a proper understanding of polyelectrolytes in their own right and Monte Carlo simulation is one of important tools that allow us to peek behind the curtain.