476236 Microfluidic Technologies in High-Throughput Chemical Screens to Decipher Genetic Basis of Behavior and Development in C. Elegans
The nematode C. elegans is of great interest to unravel fundamental biological processes common to the whole animal kingdom and to model human diseases. However, the large number of animals required per assay, complexity of protocols involved, and sensitivity to environmental perturbations render research on C. eleganstime-consuming and labor-intensive, which slows down progress and limits the scope of addressable questions.
During my post-doc at Georgia Tech, I have exploited the possibilities of microfluidics to enable traditionally challenging types of screens on first larval stage (L1) and adult nematodes. The study of first larval stage C. elegansis particularly difficult because of the small size and high motility of the animals. I overcame this challenge by developing a microfluidic platform that uses nanoliter droplets of a reversible hydrogel to offer advanced manipulation of individual animals. This work paves the way for high-throughput screening of L1 nematodes with high-resolution imaging. This will facilitate the study of numerous post-embryonic developmental cellular events such as cell differentiation and cell migration, as well as important developmental decision-making, which specifically take place during the first larval stage.
I have also developed a microfluidic platform for combinatorial chemical screening of adult nematodes. Due to the exponential increase of combinations with the number of individual components, traditional technologies require a large amount of chemicals rendering the screens impractical. I solved this bottleneck by creating a droplet-on-demand platform that enables the preparation of precise mixtures of reagents while handling nanoliter volumes and the delivery of the stimuli to the animals in a robust way. Such a platform offers the possibility of performing combinatorial screens of rare compounds. It will enable deciphering intraspecies communication by screening combinations of pheromones that are difficult to extract or synthesize. It can also benefit drug screens to identify combinatorial therapeutic strategies.
In the future, I plan on building on my experience with C. elegans and microfluidics to pursue chemical screens with droplets. In addition, I intend to expand this approach to other model organisms, which will lead to an increase in throughput of assays by several orders of magnitude and open new exciting possibilities.
During my PhD, I have taught undergrad and grad students, leading lab classes and solving-problem classes in addition to the usual TA duties (grading and helping students). I have interacted with students from a wide variety of backgrounds from which I have learned how to adapt to different learning styles. In addition, during my PhD and post-doc, I have mentored several undergrad and grad students on research projects as well.
I can teach Chemical Engineering core classes such as Numerical Methods Applied to Chemical Engineering, Mechanics of Fluids, Thermodynamics, in undergrad and I am willing to design new classes such as Microfluidics or Micro-Nano-Technologies at the graduate level.
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