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[Google Meet Link]: meet.google.com/hnd-qokh-gdb [Download title and abstract of the talk]: https://www.imsc.res.in/~asamal/seminar/AshutoshSrivastava_Aug11_2020.pdf [Abstract]: The physiology and behavior of almost all living organisms on earth is synchronized to a 24-hour solar cycle by a well-regulated molecular clock mechanism. This internal biological clock regulates a host of cellular responses to the environment, ranging from gene expression and cell division in cyanobacteria, to photosynthesis in plants and finally to the sleep/wake cycles in mammals (commonly referred as circadian rhythms). In this talk, I will present the work that we have been doing to not only enhance the understanding of molecular mechanisms regulating circadian clock [1] but also to develop therapeutic interventions to modulate the circadian rhythms in mammals [2, 3]. Using hybrid/integrative modeling, involving multiple experimental and computational methods, we have been able provide mechanistic insights into the role of cryptochromes – a core clock protein, in regulating circadian period length, thus directly relating protein structure and dynamics to in vitro and in vivo experimental observations [1]. 1. Jennifer Fribourgh*, Ashutosh Srivastava*, Colby Sandate* et al. (2020); Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing; eLife; 9:e55275 (*Equal Contribution) 2. Tsuyoshi Oshima, Yoshimi Niwa, Keiko Kuwata, Ashutosh Srivastava, et al.(2019); Cell-based screen identifies a new potent and highly selective CK2 inhibitor for modulation of circadian rhythms and cancer cell growth; Science Advances, 5, 1, eaau9060 3. Simon Miller, You Lee Son, Yoshiki Aikawa, Eri Makino, Yoshiko Nagai, Ashutosh Srivastava, et al. (2020); Isoform-selective regulation of mammalian cryptochromes. Nature Chemical Biology 16, 676-685.

In this joint work with Pramod Eyyunni and Sanoli Gun, we pursue the study initiated by P. E., M. K. Das and B. R. Patil on the study of N(x, H) which is the number of values of Euler’s totient function in the interval (x, x+H]. It is a standard result that the set of values of Euler’s function has a zero asymptotic density, which implies that N(x, H) is usually o(H). However, K. Ford, S. Konyagin and C. Pomerance have shown that N(x, H) is at most H(1/4 + o(1)) as H tends to infinity, uniformly in x. The question has been raised to know whether the constant can be replaced by 0. We give some support to the conjecture that the constant 1/4 in the above mentioned result is best possible by showing that this is the case if one takes for granted a standard conjecture of L. Dickson that suitable linear functions may simultaneously take prime values. The Google meet link for this talk is meet.google.com/frj-jmqa-pqq

[Google Meet Link]: meet.google.com/mqw-rrug-fje [Download title and abstract of the talk]: www.imsc.res.in/~asamal/seminar/UddipanSarma_Aug13_2020.pdf [Abstract]: Information encoded in the dynamics of signaling pathways often elicit critical cell fate decisions. For instance, sustained dynamics of TGF β pathway impart growth inhibition, a property abrogated in diseases like cancer.To understand how cells encode the extracellular input and transmit its information to elicit appropriate responses, we acquired quantitative time‐resolved measurements of pathway activation at the single‐cell level. We compared the signaling dynamics of thousands of individual cells and build mathematical models to understand the regulatory processes controlling the cell specific dynamics, both sustained and transient. Our combined experimental and theoretical study revealed that the response to a given dose of TGF β is determined specifically by the levels of defined signaling proteins in individual cells. Heterogeneity in signaling protein expression led to decomposition of cells into classes with qualitatively distinct signaling dynamics and corresponding phenotypic outcome. Also, negative feedback regulators promote heterogeneous TGF β signaling, as SMAD7 (a negative regulator of the pathway) knock‐out specifically affected the signal duration in a subpopulation of genetically identical cells. Taken together, our study established a quantitative framework that allows predicting and testing sources of cellular signaling heterogeneity.

More details at https://sites.google.com/view/pcseminar