PhD Defense by Pia Cordsen – Niels Bohr Institute - University of Copenhagen

Niels Bohr Institute > Calendar > NBI Calendar 2014 > PhD Defense by Pia Cor...

PhD Defense by Pia Cordsen

Dynamics of Fibril Growht and Feedback Motifs

Glucagon is a peptide hormone occuring naturally in the human blood stream but is also used medicinally by injection to treat acute hypoglycemia. Here, fibrils of glucagon are investigated by confocal microscopy at various concentrations. Basic properties of the fibrils not previously described in the literature were found, such as length distribution and apparant persistence lengths. It is found that at all concentrations, fibril growth is characterized by Poissonian stop-go dynamics where the fibril either grows (``go'') or does not grow (``stop''). A monomer-trimer model is proposed in which monomers and trimers exist in equilibrium with monomers dominating at low concentrations and trimers dominating at high concentrations. In the model, fibrils consist either of monomers or of trimers and fibril growth is inhibited when the other species binds reversibly to the fibril. Growth probability is derived from chemical reaction rates of the model, and the theoretical and experimental growth probabilities are found to be in good agreement. Speed distributions of fibrils are also analysed and found to be in good agreement with the predictions of the model.

Fibrils of the protein alpha-synuclein which are involved in Parkinson's disease are studied in vitro using total internal reflection fluorescence microscopy. Fibrillation of protein monomers is induced via two distinct pathways: Sodium dodecyl sulfate, which resulted in lumped fibrils; and seeds derived from ultra sonication of mature fibrils, which resulted in both lumped and long, straight fibrils. Previous results on real time observation of fibrils were successfully reproduced using mixed conditions of both sodium dodecyl sulfate and seeds but not when using only one of the two.

 The dynamics of a three-species network motif, consisting of a predator and two preys competing indirectly through the shared predator are investigated using symbolic dynamics, a coarse-graining method which characterizes system dynamics in terms of extrema of species densities.

The system oscillates in a large range of parameter space, and it is found that symbolic orbits reveal which of the two competitors is better and if one of them will become extinct.

Further it is found that in the range of coexistence between the two preys, the better one peaks first.