Exploring design principles of cellular information processing
In this project, I was mentored by Prof. Orkun S. Soyer and collaborating with Prof. Peter Swain and Dr. Julien Ollivier. I constructed a computer program, called BioJazz, to combine evolutionary algorithm with rule-based modelling approach (see ANC). I used this program to evolve two well-known cellular decision making dynamics, ultrasensitivity and adaptation. I found that besides allosteric regulation and zero-order ultrasensitivity, enzyme sequestration can be an evolutionary design principle for protein interaction networks to generate diverse response dynamics. Meanwhile, I discovered that bistable dynamics readily emerged from evolution of ultrasensitivity. Then I successfully identified the smallest bistable motif which requires only one kinase with two distinct conformation states and one substrate with autodephosphorylation capability. The structure pattern for bistable signalling networks suggests bistability arises from competition between futile cycles. Collaborating with serious mathematicians Prof. Elisenda Feliu, Dr. Meritxell Sáez and Prof. Carsten Wiuf, I derived unbounded multistability from increased enzyme states, either by adding more allosteric enzymes or adding more allosteric states to the single enzyme. Such multistability from compeition can not only guide synthetic biology applications in complex logic gates and state transitions but also reveal potential functional roles of cross-talks in signalling networks. This lead us to explore the design principle for bistable signaling networks. I am currently working on studying the stochasticity in reaction network motifs and searching the so-called sufficient conditions for multistable signalling network.