Seminars

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https://indico.imsc.res.in/event/5/

https://indico.imsc.res.in/event/5/

The fidelity of start codon selection is critical for synthesizing the normal proteome. The suppressor of the initiation codon (Sui¯) phenotype in yeast is a gain-of-function mutation that utilizes UUG as the initiation codon in addition to the AUG start codon and compromises translation initiation fidelity. The eIF5G31R Sui¯ mutation in the GTPase activating protein is hypothesized to utilize the UUG codon to change the proteome and adversely affect cellular physiology. By employing 2D-gel and iTRAQ proteomic techniques, we identified ~1098 differentially expressed proteins in the eIF5G31R mutant cells. Our results suggest that the eIF5G31R mutant reprograms the gene expression pattern and has a pleiotropic effect on cellular physiology, leading to nutritional and oxidative stress and sensitivity to DNA damage. To understand the mechanism of the Sui¯ phenotype of the eIF5G31R mutation, we screened for the suppressor mutations in the 18S ribosomal RNA. The C1209U change in the 18S rRNA suppresses the Sui¯ phenotype by keeping the 40S ribosomal head in the open conformation, thus bypassing the premature UUG codon recognition. The eIF2βS264Y is another Sui¯ mutation in the Ternary complex (eIF2-GTP-Met-tRNAiMet). We screened for intragenic suppressors and an extragenic suppressor mutation in the eIF2γ subunit to understand its molecular mechanism. We identified eIF2βT238A intragenic suppressor mutation and two separate eIF2γP158H and eIF2γN144D extragenic suppressor mutations. The eIF2βS264Y mutation causes premature eIF2β release, thus lowering the Ternary complex. The suppressor mutation either restores the eIF2β binding or increases the affinity for the Met-tRNAiMet to restore the Ternary complex formation. Some genes, such as GRS1 (glycyl-tRNA synthetase), use UUG as a natural start codon to initiate translation. However, the molecular mechanism of such initiation is unknown. We showed that the translation initiation from the GRS1 mRNA is not dependent on the canonical initiation factors. Some hits we obtained from our newly developed mRNA-Tethered Ribosome Interactome Profiling (mTRIP) technique will be discussed.

Quantum many-body systems undergoing phase transitions have been proposed as probes enabling beyond-classical enhancement of sensing precision. However, this enhancement is usually limited to a very narrow region around the critical point. Here, we systematically develop a modular approach for introducing multiple phase transitions in a many-body system. This naturally allows us to enlarge the region of quantum-enhanced precision by encompassing the newly created phase boundaries. Our approach is general and can be applied to both symmetry-breaking and topological quantum sensors. In symmetry-breaking sensors, we show that the newly created critical points inherit the original universality class and a simple total magnetization measurement already suffices to locate them. In topological sensors, our modular construction creates multiple bands which leads to a rich phase diagram. In both cases, Heisenberg scaling for Hamiltonian parameter estimation is achieved at all the phase boundaries. This can be exploited to create a global sensor which significantly outperforms a uniform probe. Ref.: Phys. Rev. Lett., vol. 133, 120601 (2024).

https://indico.imsc.res.in/event/5/

Pseudoexfoliation is a complex, age-related neurodegenerative disorder and a leading cause of irreversible blindness worldwide. It is characterized by the pathological accumulation of pseudoexfoliative material, primarily composed of misfolded and aggregated proteins, which obstructs aqueous humor outflow, leading to elevated intraocular pressure (IOP) and progressive optic nerve damage. While the exact etiology remains elusive, mounting evidence suggests that genetic and epigenetic factors contribute significantly to disease susceptibility and progression. Research from my lab unravels some of these intricate genetic and epigenetic regulations of genes involved in maintaining cellular homeostasis. Notably, our findings indicate significant ethnic variability in genetic susceptibility, emphasizing the need for population-specific investigations to capture the full spectrum of disease-associated genetic factors. Understanding the interplay between genetic predisposition, epigenetic modifications, and proteostasis dysfunction provides critical insights into its molecular pathogenesis. In my talk, I will focus on how our work expands the existing knowledge of pseudoexfoliation at a genomic level and highlight potential candidate genes and biomarkers that could aid in early diagnosis, risk assessment, and developing targeted therapeutic interventions.

https://indico.imsc.res.in/event/5/

The three-dimensional organization of chromatin is influenced by chromatin-binding proteins through both specific and non-specific interactions. However, the roles of chromatin sequence and the interactions between binding proteins in shaping chromatin structure remain elusive. By employing a simple polymer-based model of chromatin that explicitly considers sequence-dependent protein binding and protein?protein interactions, we elucidate a mechanism for chromatin organization. We find that tuning protein?protein interactions and protein concentration is sufficient to either promote or inhibit chromatin compartmentalization. Moreover, chromatin sequence and protein?protein attraction strongly affect the structural and dynamic exponents that describe the spatiotemporal organization of chromatin. Strikingly, our model?s predictions for the exponents governing chromatin structure and dynamics successfully capture experimental observations, in sharp contrast to previous chromatin models. Overall, our findings have the potential to reinterpret data obtained from various chromosome conformation capture technologies, laying the groundwork for advancing our understanding of chromatin organization.

https://indico.imsc.res.in/event/5/

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https://indico.imsc.res.in/event/5/

TBA

https://indico.imsc.res.in/event/5/

We begin with a review of the modern perspective on graph coloring which appeared in the work of Kronheimer-Mrowka and Khovanov-Robert. Next, we outline how the work of Treuman-Zaslow and Caslas-Zaslow lead to seeing graph coloring as topological defects labelled by the elements of Klein-Four Group. This highlights the quantum nature of graph coloring, namely, it satisfies the sum over all the possible intermediate state properties of a path integral. In our case, the topological field theory (TFT) with defects gives meaning to it. This TFT has the property that when evaluated on a planar trivalent graph, it provides the number of Tait-Coloring of it. Defects can be considered as a generalization of groups. With the Klein-four group as a 1-defect condition, we reinterpret graph coloring as sections of a certain cover, distinguishing a coloring (global-sections) from a coloring process (local-sections), and give a new formulation of some of Tait's work.

https://indico.imsc.res.in/event/5/

Fast radio bursts (FRBs) are prolific transient signals of uncertain origin detected by radio telescopes worldwide. We apply Topological Data Analysis (TDA), a branch of mathematics that studies the shape and structure of data, to a large sample of FRBs. We use the Mapper algorithm, a TDA method that constructs a simplicial complex approximating the shape of the data set, to visualize its topological structure. We find a clustering of FRBs into two groups according to their repetition rate and a robust structure reflecting their morphological structure and energy. These results suggest that there are two physically distinct populations of FRBs. We also produce a list of candidate non-repeating FRBs that could be repeaters based on their proximity to known repeaters in the Mapper graph. Our work demonstrates the potential of TDA as a powerful tool for exploring and understanding the nature and origin of FRBs. In this talk, I will discuss the TDA method and three use cases of FRBs as a cosmological probe.

https://indico.imsc.res.in/event/5/

https://indico.imsc.res.in/event/5/

We consider the following question. Given a global transition system TS over a set of actions A, together with a distribution of A into local components (A_1,...,A_k), does there exist a distributed transition system over (A_1,...,A_k) that is "behaviourally equivalent" to TS? We focus on two variants of distributed transition systems --- loosely cooperating systems and synchronously communicating systems. For behavioural equivalence, natural choices are language equality and bisimulation. For some combinations of system model and behavioural equivalence, the problem has been solved decades back. Somewhat surprisingly, other versions of the problem still remain open. We will survey the state of the art.

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