Oberseminar zur Numerik im SoSe 2016
Im Rahmen des Oberseminars der AG Numerik wird
Herr Dr. Peter Rashkov, Computational Biology Lab, University of Exeter, am Mittwoch, den 25. Mai 2016, zum Thema
Appearance of Hormesis in a Simple Enzyme Kinetic Model
vortragen.
Abstract. Hormesis is a therapy response characterised by stimulation of activity at low doses and inhibition at high doses. In contrast to the downward-sloping dose response curves that have almost become traditional in drug discovery, the hormetic (or biphasic) dose response curve has an inverted U-shape. This paradoxic pheno- menon was observed more than 100 years ago in the context of toxins, and initially was met with skepticism, but ever since it has been recognised in a wide range of situations: in antibiotic and antifungal and recently also in cancer therapy. Despite the large implications for therapy design, the mechanisms behind hormesis remain for the most part poorly understood. I will present a mathematical model based on first principles that is able to produce hormesis for the action of a kinase inhibitor in the MAPK signalling pathway. This pathway is important because it often becomes deregulated in cancer cells causing uncontrolled cell proliferation and metastasis. The model demonstrates that the causes behind the phenomenon could be purely bioche- mical and, more importantly, it does not rely on ad-hoc assumptions commonly used in other models for hormesis. It also sheds light on why hormesis could be masked in population-level biochemical assays used in drug discovery.
This is joint work with Ian Barrett and Claus Bendtsen (AstraZeneca, Cambridge, UK) and Ivana Gudelj (University of Exeter).
Der Vortrag findet um 14:15 Uhr im Seminarraum 06D10 am Fachbereich Mathematik und Informatik, Hans-Meerwein Str., Lahnberge, statt.
Es l¨ad ein die AG Numerik
