How a dynamical model can help to predict phenotype from genotype?
- 14:00 17th May 2013 ( week 4, Trinity Term 2013 )Room L1 of the Mathematical Institute
Understanding how the phenotype of a disease arises from individual molecules and their interactions is a primary challenge in biology that mathematical approaches are poised to tackle. Protein folding diseases are an ideal system to investigate the relationship between genotype and phenotype. A protein folding disease can occurs when a specific protein fails to fold into its correct functional state as a result of a mutation in the protein. In this seminar, I present a mathematical model of the protein expression and processing which we have used to investigate how the protein folding disease phenotype can be manifested. Using a continuous flow reactor model for protein processing, we found that the onset and rescue from a protein folding disease can be controlled by some combination of the transition time of proteins in the reactor, the ratio of wild-type and mutant proteins inflow rates in the reactor and a chemical interaction parameter between wild-type and mutant proteins. Our analysis reveals potential therapeutic strategies targeting the modulation of protein folding diseases, which have been tested in cellular and animal models of Mutant INS-gene Induced Diabetes of Youth and Congenital Hypothyroidism with deficient thyroglobulin.