Input-Output Functions to Describe Gene Regulatory Networks
Can gene regulatory networks be described like electronic circuits? With Elizabeth Eck at UC Berkeley, I am developing an input-output functional description of gene regulatory networks in the context of the developing fruit fly embryo. By experimentally measuring both transcription factor (i.e. input) concentrations and transcription activity (i.e. output), we can compare our data with various theoretical descriptions and constrain the space of possible classes of models. Unlike previous work, which mainly relies on static data taken at fixed timepoints in embryonic development, our experiments capture the full spatiotemporal dynamics of the system, which have the capacity to reveal interesting underlying mechanisms that cannot be seen with static measurements.
Nonequilibrium Processes in Transcription Regulation
With Elizabeth Eck at UC Berkeley, I am studying signatures of nonequilibrium behavior in transcription initiation. We have recently discovered evidence of nonequilibrium transcriptional regulation in the context of the P2P promoter and enhancer system in the fruit fly. Controlled by the Bicoid and Zelda transcription factors, we found that in the absence of Zelda protein, the resulting transcriptional output of P2P could not be described by any equilibrium model of transcription. In fact, the data could only be explained with a model invoking energy expenditure out of equilibrium. Such analysis relied on highly dynamic measurements of both input transcription factor and output transcription that revealed signatures of nonequilibrium mechanisms, and suggest that these nontrivial behaviors require time-resolved data.
Correlations in Sister Chromatid Transcription
With Meghan Turner and Liya Oster, I am developing a system to visualize transcription on individual sister chromatids in single cells using two colors and in real time. Previous experiments either provided static measurements or could only utilize a single color, preventing accurate observations of sister chromatids that were too close together in space. With this two-color experimental scaffold, we aim to measure dynamic transcriptional outputs of individual sister chromatids to see what (if any) correlations exist between the chromatids, especially as a function of the distance between them.
DNA Accumulation at Heated Air-Water Interfaces and the Origins of Life
With Prof. Dieter Braun at the LMU in Munich, I discovered that DNA, when placed in microscale channels filled with water, spontaneously accumulates at air-water interface (e.g. bubbles) when the system undergoes heating. Further work showed that other biomolecules also accumulated, such as lipids and RNA precursors. In fact, vesicle structures can form as a result of this accumulation and trap nucleic acids inside in a protocell-like fashion. This surprising discovery holds implications for the origins of life, as many theories of early evolution require biomolecules such as DNA to somehow accumulate to chemically relevant concentrations amidst a lifeless Earth.