CoSy Lunch Seminar
- Datum: –13.00
- Plats: Ångströmlaboratoriet Å4003
- Föreläsare: Dr. Sturrock, Department of Physiology, Royal College of Surgeons in Ireland
- Arrangör: CIM
- Kontaktperson: Joel Dahne
- Telefon: 0762020507
The influence of nuclear compartmentalisation on stochastic dynamics of self-repressing gene expression; Speaker: Dr. Sturrock, Department of Physiology, Royal College of Surgeons in Ireland
Speaker: Dr. Sturrock, Department of Physiology, Royal College of Surgeons in Ireland
Title: The influence of nuclear compartmentalisation on stochastic dynamics of self-repressing gene expression
Time: 12:15 -- 13:00
Dr. Sturrock is a Lecturer in Computational Biology in the Department of Physiology at the Royal College of Surgeons in Ireland. He received his B.Sc. in Applied Mathematics from the University of Dundee in 2009 and then stayed on to complete his PhD under the supervision of Prof. Mark Chaplain in 2013. His thesis research examined spatio-temporal models of gene regulatory networks containing negative feedback loops. Dr. Sturrock then completed a Post Doctoral Research Fellowship at the Mathematical Biosciences Institute within The Ohio State University. Here he worked on projects in macromolecular crowding under the mentorship of Prof. Radek Erban and cell polarization under the mentorship of Dr. Adriana Dawes. Finally, he completed a second postdoc at Imperial College London within a synthetic biology group led by Prof. Mark Isalan where he worked on projects in emergent gene expression and synthetic Turing pattern formation.
Gene expression is an inherently noisy process. This noise is generally thought to be deleterious as precise internal regulation of biochemical reactions is essential for cell growth and survival. Self-repression of gene expression, which is the simplest form of a negative feedback loop, is commonly believed to be employed by cellular systems to decrease the stochastic fluctuations in gene expression. When there is some delay in autoregulation, it is also believed that this system can generate oscillations. In eukaryotic cells, mRNAs that are synthesised in the nucleus must be exported to the cytoplasm to function in protein synthesis, whereas proteins must be transported into the nucleus from the cytoplasm to regulate the expression levels of genes. Nuclear transport thus plays a critical role in eukaryotic gene expression and regulation. Some recent studies have suggested that nuclear retention of mRNAs can control noise in mRNA expression. However, the effect of nuclear transport on protein noise and its interplay with negative feedback regulation is not completely understood. In this talk, I will present four different simple models of gene expression. Through the use of stochastic simulations and applying the linear noise approximation to the corresponding chemical master equations, I will present an investigation of the influence of nuclear import and export on noise in gene expression in a negative autoregulatory feedback loop. I will first present results consistent with the literature, i.e., that negative feedback can effectively buffer the variability in protein levels, and nuclear retention can decrease mRNA noise levels. I will then go on to show that when negative feedback is combined with nuclear retention, an amplification in gene expression noise can be observed and is dependent on nuclear translocation rates. Finally, I will end with a discussion of the effect of nuclear compartmentalisation on the ability of self-repressing genes to exhibit stochastic oscillatory dynamics.