• Tracking the molecular players in neurodegenerative disorders

    In the department of chemical sciences, we investigate biophysically tractable yet biologically interesting systems, using (mostly) spectroscopic and imaging tools, most of which we build ourselves. Our recent focus has been on two problems: protein misfolding/aggregation, and vesicular neurotransmission....

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  • Turn-on Sensors for in vivo Imaging

    The quest for unraveling fundamental biological pathways relies heavily upon the ability to precisely visualize strategic molecular players in vivo. Our group works at the interface of synthetic chemistry, molecular biology, and imaging, to develop molecular probes which give a specific ‘ON’ response only in presence of the bio-molecule of interest....

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  • Deciphering the Catalytic Activity of an Orphan P450 enzyme

    A systematically screened several fatty acids (saturated and monounsaturated) for their potential as substrates for CYP175A1 shows that the wild type enzyme could catalyze the reaction of mono-unsaturated fatty acids but not of saturated fatty acids...

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  • Perfecting Imperfection: Defected Nanosilica can transform COto Fuel without any metal and ligands. 

    Using the defect engineering approach, we develop metal-free–ligand-free nanocatalysts, which convert CO2 to methane at the significant rates, scales, and stabilities.....

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  • Title : To be announced

    Abstract :

About the Department

Scientists at the DCS explore the link between living systems and the physical laws that govern nature. They study molecules ranging in size as small as water and as large as a virus. The laws that govern interaction in molecules are best studied in well-defined and isolated small molecules. This information becomes applicable to design novel materials with exotic properties, of value to chemical and solar energy industries and to medical applications. To understand working of biological systems, studies are made on structure, dynamics and function of biological molecules. TIFR is a leader in state-of-the-art experimental techniques such as high field NMR, ultrafast lasers and single molecule methodologies.

Calendar

  • Seminar by Dr. Adusumalli Srinivasa Rao, University of Cambridge, UK on January 18, 2022 at 4.00 pm via Zoom Platform

    Title :

    Chemical tools for selective probing of protein activity and degradation of biomolecules

    Abstract :

    Technological advancement often leads to major discoveries in chemical biology research. The functional diversity of biomolecules and their impact on vital biological processes inspire the development of methods for the precision engineering of these molecules. The growing interest in selective labeling and/or degradation of biomolecules has emerged from the necessity to understand and regulate their structure and function. During my talk, I will discuss how chemical tools can enable the selective tuning/degradation of biomolecules for their therapeutic applications. First, I will introduce a new electrophilic warhead to deliver the cysteine conjugates for protein therapeutics. Besides, the development of biorthogonal chemical reactions has been an unprecedented opportunity for the study and manipulation of biological processes within living systems. Precise perturbation of protein activity with high selectivity is crucial to probe and control dynamic protein activity. The development of proximity driven reversible covalent orthogonal strategy will enable the loss and gain of the function of protein with high selectivity to study dynamic cellular processes.

    Methods for target protein degradation have advanced the field of drug discovery. In particular, PROTACs and molecular glues gained much attention during the last decade. However, the PROTACs require strong affinity ligands for both E3 ligase and target protein whereas the discovery of most of the molecular glues was serendipitous. Hence, there is an unmet need to develop new technologies. A novel rational design of reversible covalently binding PROTACs (RECOBIN-PROTACs) will be discussed for target protein degradation. Also, another reversible/irreversible covalent strategy will introduce a new modality on PROTACs to generate a new class of Electrophilic-PROTACs that does not require the need of ligand for protein degradation. This new modality enhances the protein-protein interaction between E3 ligase and protein and it also stabilizes the ternary complex formation which plays a key role in the efficient degradation of the protein. Finally, targeted degradation of RNA species plays a key role in numerous cellular mechanisms. The specific interactions of enzyme with RNA gives an ample opportunity to develop small molecule degraders. So the principles of small molecule degraders that take advantage of specific enzyme-RNA interactions and modified bases on RNA to induce the degradation of specific RNA will be outlined.

  • Seminar by Dr. Adusumalli Srinivasa Rao, University of Cambridge, UK on January 17, 2022 at 4.00 pm via Zoom Platform

    Title :

    Chemical technologies for precision labeling of native proteins

    Abstract :

    Single-site protein modification impacts diverse aspects of Science at the interface of biology, chemistry, biomaterials, and biologics. The prominent way to access such protein conjugates is through bio-synthetically pre-engineered proteins with un-natural amino acids or fragments. Unfortunately, these methods do not operate with native proteins leaving an enormous technological void. The solution to this challenge would require a chemical transformation that can allow single-site protein labeling, regulation of the site-of-labeling, and operate with multiple proteins. During my talk, I will present the chemical tools for precession engineering of proteins. The challenges related to reaction kinetics, chemoselectivity, and site-selectivity for single-site labeling of proteins will be addressed. These chemical methods can render site-selective N-terminus labeling of proteins and also can distinguish N-terminus residues for site-specific labeling. In particular, I would like to bring your attention to Gly-Tag® and Linchpin Directed Modification (LDM®) technologies that led to residue-specific labeling and site-selective labeling of proteins respectively. The native proteins can now be labeled with absolute precision enabled by a modular chemical platform (LDM®). The functional groups introduced by labeling open the potential for the orthogonal late-stage installation of an affinity tag, NMR tag, and a fluorophore. These chemical technologies are operationally simple, deliver ordered immobilization, and analytically pure probe tagged proteins. The LDM technology enabled the synthesis of homogeneous antibody-drug conjugates that exhibits highly specific antiproliferative activity toward HER-2 positive SKBR-3 breast cancer cells. Besides, I will discuss the first general method for chemoselective functionalization of serine residue which is rarely chosen as a handle for selective derivatization. Finally, I will end my talk with the development of new PSI-reagents that can render selective transformation of serine residue into Dha formation, a post-translational modification.

  • Seminar by Dr. Amrit Venkatesh, Laboratory of Magnetic Resonance, EPFL, Switzerland on January 10, 2022 at 4.00 pm in AG-66

    Title :

    Sensitizing solid-state NMR using fast magic angle spinning and dynamic nuclear polarization

    Abstract :

    NMR is a powerful atomic-level characterization technique but it suffers from an intrinsically poor sensitivity, limiting its application to common spin-1/2 isotopes such as 1H, 13C, 15N, 29Si, 31P etc. Whereas, over 75% of the periodic table consists of unreceptive nuclei that are rarely studied using NMR due to the lack of sensitive approaches. Fast magic angle spinning (MAS) enables the observation of the sensitive 1H spins in solids by narrowing 1H NMR lineshapes. This allows the use of 1H spins as ‘spies’ for indirect detection of other nuclei, much like solution NMR spectroscopy. Here, we will demonstrate how 1H detection methods in solids allow meaningful chemical information to be extracted from low gyromagnetic ratio nuclei, half-integer quadrupolar nuclei and the spin-1 isotope 14N.

    The sensitivity of NMR can alternatively be drastically improved using dynamic nuclear polarization (DNP) from nearby electron spins. Gd(III) complexes are attractive exogenous PAs for MAS DNP due to their high chemical stability, but they are infrequently used for DNP due to their limited DNP efficiency. Here, we will establish a model that correlates the DNP enhancements provided by Gd(III) complexes with zero-field splittings. These results will pave the way for the development of efficient Gd(III) polarizing agents.

    Finally, the application of these state-of-the-art solid-state NMR techniques to characterize small molecule pharmaceuticals, organometallic compounds and semi-conducting nanomaterials will be demonstrated.

  • Seminar by Dr. Tushar Debnath, Ludwig - Maximilians - University, Munich, Germany on December 21, 2021 at 4.00 in AG-66

    Title :

    Vibrational Wave-packet Dynamics to Unravel the Bio-solid Coupling

    Abstract :

    The coherent interaction between a light photon and a semiconductor provides fundamental insights into solid-state physics. Incorporation of biologically relevant molecules, such as amino acids, as a capping agent in fluorescent semiconductor nanocrystals (NCs), can make them suitable as fluorescent bioimaging probes. Unraveling the strain-induced ultrafast lattice rearrangement dynamics due to coherent phonon formation in bio-functionalized semiconductor NCs can open new insights.

    Continuing from the first talk, where mainly I will talk about the excitonic properties of semiconductor nanomaterials, in the second talk I will show the vibrational coherences in bio-functionalized nanomaterials. Before going into my future research plan, I will show some of our very recent work on coherent phonon dynamics in perovskite NCs. Biomolecules with several functional moieties will supposed to influence the coherent phonon dynamics to a larger extend due to enhance bio-solid coupling. With this idea in mind, I will then establish my future research plan on bio-functionalized Cd- and Pb-free non-toxic nanomaterials.

  • Seminar by Dr. Tushar Debnath, Ludwig - Maximilians - University, Munich, Germany on December 20, 2021 at 2.00 in AG-66

    Title :

    Ultrafast Photophysical Dynamics of Energy Harvesting Nanomaterials and Bio-relevant Molecules

    Abstract :

    It has been more than 30 years that the field of nanocrystal (NC) has emerged, driven by the attractive physics due to its strong confinement, along with several prospective applications. To fully realize the potential of the NCs, it is of utmost importance to study the fundamental of the exciton relaxation-recombination dynamics which often falls in the femto (10-15 s) - to nanosecond (10-9 s) timescale. Ultrafast optical spectroscopic techniques offer a detailed understanding of exciton relaxation and recombination dynamics.

    In this talk, I will focus on the ultrafast excitonic properties of the recently emerged undoped and doped perovskite NCs. Then I will talk about the ultrafast charge transfer dynamics of undoped and doped II-VI quantum dot (QD) materials on the relevance of solar energy harvesting. Finally, I will briefly introduce the elementary processes that accompany the interaction of ionizing radiation with biologically relevant molecules in an aqueous solution. Using femtosecond coherence spectroscopy, I will elucidate the vibrational wave packet dynamics that follow the photodetachment of amino acids in an aqueous solution.