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Our lab is interested in the systems biology and evolution of epigenetic switches (bistability) and clocks (oscillators) in gene regulatory networks. We use experiment and theory, biology and physics, systems and synthetic biology to study the cell cycle, metabolic rhythms, and circadian clocks. How do oscillators with different frequencies co-exist in the same cell? Are there mechanisms and regulatory principles that ensure functional harmony between oscillators?

BayFish: Bayesian inference of transcription dynamics from population snapshots of single-molecule RNA FISH in single cells

screen-shot-2017-09-12-at-10-49-05-amSingle-molecule RNA fluorescence in situ hybridization (smFISH) provides unparalleled resolution in the measurement of the abundance and localization of nascent and mature RNA transcripts in fixed, single cells. Mariana developed a computational pipeline (BayFish) to infer the kinetic parameters of gene expression from smFISH data at multiple time points after gene induction. Given an underlying model of gene expression, BayFish uses a Monte Carlo method to estimate the Bayesian posterior probability of the model parameters and quantify the parameter uncertainty given the observed smFISH data. This has been a fun and fruitful collaboration with the Anne West lab in Neuroscience at Duke!

Gomez-Schiavon M, Chen LF, West AE, Buchler NE.  BayFish: Bayesian inference of transcription dynamics from population snapshots of single-molecule RNA FISH in single cells.  Genome Biology 18: 164 (2017)

Gene duplication and co-evolution of G1/S transcription factor specificity

screen-shot-2017-05-23-at-3-41-41-pmRead our latest work that builds upon our growing expertise in cell cycle genomics and the evolution of the G1/S regulatory network in Fungi. This manuscript studied the evolution of duplicated G1/S transcription factors (SBF and MBF) in the budding yeast S. cerevisiae by examining 16 different chimeric transcription factor complexes containing the DNA binding domains from different fungi species. Our data shows that while SBF is the likely ancestral regulatory complex, the ancestral DNA binding element is more MCB-like. G1/S network expansion after gene duplication took place by both cis– and trans– co-evolutionary changes in closely related but distinct regulatory sequences. This was a fun collaboration with Amir Aharoni (Ben Gurion University) and Rob de Bruin (University College London)

Hendler A, Medina EM, Kishkevich A, Abu-Qarn M, Klier S, Buchler NE, de Bruin RAM, Aharoni A. Gene duplication and co-evolution of G1/S transcription factor specificity in fungi are essential for optimizing fitness.  PLoS Genetics 13: e1006778 (2017)