Browsing by Author "Onuchic, José"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item Construction of an Effective Landscape for Multistate Genetic Switches(American Physical Society, 2014) Lu, Mingyang; Onuchic, José; Ben-Jacob, Eshel; Center for Theoretical Biological PhysicsMultistate genetic switches play a crucial role during embryonic development and tumorigenesis. An archetypical example is the three-way switch regulating epithelial-hybrid-mesenchymal transitions. We devise a special WKB-based approach to investigate white Gaussian and shot noise effects on three-way switches, and construct an effective landscape in good quantitative agreement with stochastic simulations. This approach allows efficient analytical or numerical calculation of the landscape contours, the optimal path, and the state relative stability for general multicomponent multistate switches.Item Data Driven Modeling of Proteins(2019-03-20) Chen, Justin; Clementi, Cecilia; Onuchic, JoséProteins are tiny molecular machines that perform the vast majority of the functions in living cells. In order for the protein to perform its function, it has to be able to fold from a disordered coil into a specific compact structure. Two new computational methods are developed that take advantage of the large amount of data generated in both experiments and computer simulations in order to better understand how proteins work. The first method (pyODEM) improves the modeling of proteins on the global scale, while a second method (pyFrustration) probes the protein's local frustration that might impede the folding process. Use of these methods allows us to construct more dynamically accurate protein models and improves our understanding of how a protein folds and performs its function.Item Turning Oscillations Into Opportunities: Lessons from a Bacterial Decision Gate(Nature Publishing Group, 2013) Schultz, Daniel; Lu, Mingyang; Stavropoulos, Trevor; Onuchic, José; Ben-Jacob, EshelSporulation vs. competence provides a prototypic example of collective cell fate determination. The decision is performed by the action of three modules: 1) A stochastic competence switch whose transition probability is regulated by population density, population stress and cell stress. 2) A sporulation timer whose clock rate is regulated by cell stress and population stress. 3) A decision gate that is coupled to the timer via a special repressilator-like loop. We show that the distinct circuit architecture of this gate leads to special dynamics and noise management characteristics: The gate opens a time-window of opportunity for competence transitions during which it generates oscillations that are turned into a chain of transition opportunities – each oscillation opens a short interval with high transition probability. The special architecture of the gate also leads to filtering of external noise and robustness against internal noise and variations in the circuit parameters.