We have investigated how to use statistics to quantitate the Central Dogma: DNA makes mRNA, and mRNA makes protein, one of the most fundamental principles in modern biological sciences. There are two key synthesis steps: transcription (information flow from DNA to mRNA) and translation (information flow from mRNA to protein). In addition, mRNA and protein molecules are degraded (i.e., destroyed), making four steps in total. In the past seven years, I collaborated with Dr. Mark Biggin, a biochemist at Lawrence Berkeley National Laboratory, to examine the question—which of the four steps are most important in determining protein abundance. Our collaboration was fruitful: we published four papers [1, 2, 3, 4] in high-impact journals including Science, Nucleic Acids Research, and Genome Biology, our result was included in an undergraduate textbook, the eighth Edition of Molecular Cell Biology, and we had successes in funding applications including the Johnson & Johnson Women in STEM2D Award and the Keck Foundation Junior Faculty Award.

Specifically, in [1, 2] we used statistics to quantify the relative contributions of transcription and translation in determining protein abundances in animal cells. By re-analyzing existing large-scale transcriptomic and proteomic data, we showed that transcription is the dominant step, in contrast to the claims of many papers over the last decade that had suggested that translational control plays the larger role. Our continuing work in [3] shows that decomposing translational rate into RNA dependent and independent components further reveals mechanisms behind translational control. Furthermore, in our recent work [4] published in Genome Biology, we elucidated a conserved, quantitative mechanism in five eukaryotic species about how mRNA sequences determine their translation rates.

References: