"What you can not create, you can not understand.", Richard Feynman
The book 'What is life' by Professor Erwin Schrodinger invigorated my scientific interest in synthetic biology. I was motivated to learn about how Professor Schrodinger applied physical reasoning to biological systems, in the year 1944 when the fields 'synthetic biology' and 'systems biology' were non-existent. The explanation on how ordered biological systems arise from disordered systems interested me and I started pondering on how I can decipher biological systems using my engineering skills.
I entered the synthetic biology field with a Bachelor's degree in Civil Engineering from the National University of Singapore (NUS) and a Master of Science degree from the Singapore-MIT Alliance. I am particularly strong in mathematics and numerical algorithms, which I take as fundamental to every branch of science and engineering. With the strong background in physical sciences, I hope to apply such quantitative methods to understand biological systems.
A biological question that has always intrigued me is how do cells process a wide range of extracellular and intracellular oscillations? Extracellular oscillations include environmental changes such as temperature, nutrient, and water. Intracellular oscillations involve concentration changes of molecular species such as proteins and metabolites, with specific periods ranging from seconds in calcium signaling pathways, to minutes in Notch segmentation clocks and yeast respiratory cycles, and hours in circadian rhythms. To maintain normal physiology, cells need to respond to the oscillations reliably. Cells can respond to the oscillations by at least one way, which is by regulating gene expression levels. The regulation is carried out by a complex network of genes that interact through directed transcriptional regulation.
Importantly, oscillating stimuli have been shown to impact natural signaling networks. For instance, oscillations of NaCl modulate osmo-adaptation pathways of Saccharomyces cerevisiae; oscillations of circadian master regulator KaiC cause oscillations of gene expression noise in downstream pathways. Even though the impact of oscillating signals is evident, it remains elusive as to how different gene networks process these signals.
My long term goal is to elucidate the response of gene networks to oscillating environments at the systems level. The specific hypothesis behind my PhD study is that gene networks can modulate single cell response to oscillating environments. To reduce complexity, I first conceptualize gene networks as interconnected network motifs, such as feedback or feedforward regulation. Next, I focus on these network motifs and quantify their fidelity and speed of information transmission using synthetic gene circuits (in bacteria Escherichia coli). The quantification is based on single cell measurements in oscillating environments by using time lapse microscopy.
Lastly, I believe that by revealing how gene networks impact the transmission of oscillating signals, my work may provide fundamental insights into the design laws of biological circuits.