Sauer Group, Allosteric Regulation, Metabolic Network, Kinetic Modeling

Tutors:

Elad Noor ()

Dimitris Christodoulou ()

Duration: 3 months

Start: Today

Keywords: allosteric regulation, dynamic systems, kinetic modeling, data mining, stochastic processes

Background

The allosteric regulation of enzymes by small molecules plays an essential role in the cells' fast response to abrupt environmental changes and in its homeostasis generally. For instance, many amino-acid biosynthesis pathways are allosterically inhibited by their product in order to save precious carbon and energy resources when the biosynthesis isn't needed. During the last decade, thanks to high-throughput methods, we are experiencing an explosion of information regarding allosteric inhibitors and activators so that tens of thousands of such effectors are known today, in many different organisms.

Your project

This project is planned to be mainly computational and its goals entail i) analysis of the topological, genetic and chemical characteristics of enzymes that have been reported to be allosterically regulated  ii) analysis of the chemical characteristics of metabolites that are known to allosterically regulate enzymes iii) retrieval and statistical analysis of the K_i values of known allosteric effectors in Central Carbon Metabolism of E. coli, ultimately iv) the in silico design and reconstruction of a consensus kinetic model of E. coli Central Carbon Metabolism, including the known allosteric interactions and kinetic parameters found in literature and v) with the aid of the model try to unravel the role and function of allosteric interactions in certain conditions and perturbations.

You will learn how to mine existing databases (e.g. BRENDA, KEGG), to generate hypotheses from high-dimensional data, analyze network information using topological features in the context of protein-metabolite interactions, how to design and implement kinetic models and how to explore their properties. Furthermore, you will gain experience in (deterministic and/or stochastic) simulation of complex systems and in the analysis of their structural properties.

This project is planned as a semester project (3 months) and is a unique opportunity for you to perform state-of-the-art computational work in an experimentally focused lab. This semester project fits you if you would like to challenge your computational skills into unraveling chemical and topological aspects of the complex allosteric level regulation. Experience in programming (Perl/Python/Matlab) is required.