Research

 


Overview

 


We are interested in quantitative studies of biological systems. We apply, develop and integrate theoretical, computational and experimental methods to address key biological questions. We believe that an interdisciplinary approach focusing on quantitative questions at a systems level will uncover new biological principles and help us to better understand complex disease and design new therapeutic strategies. Our current research areas include cell cycle regulation, cellular decision-making, the relationship between function and topology in biological networks, developmental landscape, information processing in biological systems and network-based complex disease mechanism.




Cell cycle regulation

 


The eukaryotic cell cycle is a highly conserved process and its malfunction is a hallmark of cancer. This complex process of cell replication and division consists of a series of transitions between distinct events, some of which are guarded by checkpoints. We are interested in quantitative mechanisms and general principles in the design of the system to ensure precise, robust and decisive transitions and how perturbations/mutations can compromise the system. Using budding and fission yeasts as the model organism, we investigate these questions with a combination of mathematical modeling, yeast genetics, time-lapse fluorescent microscopy, single cell assays, and microfluidic devices.




Network function and topology

 


There is a close relationship between a network's function and its architecture (topology). Understanding this function-topology mapping would provide a framework to functionally classify and understand the complex biological networks, as well as a design table for synthetic biology. Using computational methods, we have been investigating the function-topology relationship for small functional modules. An example is the biochemical adaptation circuits. We have identified all the circuit architectures that can perform adaptation robustly. Despite of the diversity of biochemical networks, there are only two core solutions to achieve perfect adaptation. Reccently we studied minimal circuits to generate cell polarity, in which computational method is combined with that of synthetic biology to identify and demonstrate the core topologies of cell polarity.




Cellular decision-making and fate determination

 


Cells have to make various decisions in response to external and/or internal cues, and often make fate choices. Examples range from stress response, development to stem cell differentiation and reprogramming. We are interested in strategies, mechanisms, information flow, general principles and the mathematical framework in these systems and processes.