I plan to use the K25 award at the associate professorship level to complete my transition from theoretical physics into quantitative systems biology. My immediate goal is to deepen my understanding of biology and the related chemistry. I plan to achieve it through my continuous development of a new high throughput label-free protein chip platform. This experimental route to biology has several advantages: This high throughput protein chip is very desirable in the current molecular biology research; The development has given me first-hand information on the state-of -art of experimental biology, on how the systems biology experiments are designed, and on how the data are taken and analyzed. In addition, it immediately makes use of my physics and material sciences knowledge in the designing of the instrument and of the data analysis tools. After becoming well versed in biology, I will investigate the computational side of systems biology, such as the theoretical description of the gene regulatory networks. ? ? During the award period I propose to have three intensive training rotations in yeast biology, organic chemistry, and developmental biology laboratories to learn the related modem molecular biological experimental techniques. ? ? My choice of the surface plasmon resonance technology research plan is based the following advantageous position: 1). The team led by myself has made the technical breakthroughs that put us right in the position to explore the high throughput protein chip; 2). Surface plasmon resonance technology is a most promising candidate for the high throughput protein chip, because: a). It is one of the most sensitive detection methods; b). Crude prepared protein extract can be used, which greatly simplifies the detection process; c). It can perform a real time detection, yielding vital kinetic information such as affinity for the protein-protein interaction; d). The surface plasmon resonance detection is non-label, which avoids the complicated labeling procedure as well as the risk of denaturing proteins due to labeling; e). The detection can be quantified, because the surface plasmon resonance detects the change of refractive index due to the total amount of materials on the surface. ? ? Biological models studied at the Institute for Systems Biology will be used to test and validate the label free protein chip platform during its development. Additional funds will be aggressively sought to support the project. The execution of the research plan will provide the needed opportunity to deepen my understanding of systems biology. ? ? ?
