Chieh joined School of Biosciences as the Eastern ARC Research Fellow in synthetic biology in March 2015.
Chieh did his BSc studies in National Taiwan University in 2002. He continued his postgraduate studies in the Molecular Biology Program, University of Goettingen, Germany, and received an MSc in Biochemistry mentored by Dr Jobst Landgrebe (2004-2006). He developed a strong interest in cell biology and contributed to the early findings in exosome biogenesis during his PhD curriculum in Prof Mikael Simons' lab at the Max-Planck Institute for Experimental Medicine (2006-2010). Later he broadened his research interest into molecular systems biology. He joined Prof Attila Becskei's group in University of Zurich (2010-2011) and University of Basel (Biozentrum, 2011-2015), Switzerland and was awarded the long-term fellowship from Human Frontier Science Program (2011-2014) to study system stability, cellular memory, and stochastic/deterministic factors in transcriptional auto-regulatory circuits.
The Hsu group applies synthetic approaches to bridge cell biology and molecular systems biology for quantitative studies in living systems.
Currently the group is establishing two major synthetic frameworks using the yeast Saccharomyces cerevisiae:
1) Positive feedback loops and protein membrane domains. In eukaryotic cells, organelles exchange materials in membranous vesicles in a process called intracellular membrane trafficking. To ensure proper sorting, a given membrane needs to be identified before assigned to transport machineries. The protein family, small GTPases, establish membrane identity on various organelles and vesicles. They act as the molecular switches and once activated, they are attached to the membrane and recruit the same molecular to the surrounding membranes. To quantitatively understand this complicated process in which diffusion plays a key role, synthetic model systems are being made to dissect how individual reaction affects the overall kinetics and dynamics.
2) Evolution of switching rate between cell fates. During evolution, positive feedback often emerges in gene regulation and leads to a switch like response that allows activating certain genes only when the environmental stimuli reach a certain threshold. However, such feedback systems can also result in a phenomenon called cellular memory, or hysteresis. In this case, the cellular response to an environmental stimulus depends on whether the cell has been activated before: a previously activated cell stays activated and vice versa. Obviously, cellular memory slows down or even prevents proper response, which can cause adaptation disadvantage. A synthetic system is being established to study how such switching rates affect fitness and how switching rate evolves in a population under rapid and extreme environmental change.
Visit Chieh's page on the University of Kent website