A5027896996- Adipose Tissue and Metabolism
- Nuclear Structure and Function
- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
- Lipid metabolism and biosynthesis
- GDF15 and Related Biomarkers
- Adipokines, Inflammation, and Metabolic Diseases
- Microbial Metabolic Engineering and Bioproduction
- Fibroblast Growth Factor Research
- RNA modifications and cancer
- Malaria Research and Control
- Glioma Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- interferon and immune responses
- Cellular transport and secretion
- Biotin and Related Studies
- Epigenetics and DNA Methylation
- Internet Traffic Analysis and Secure E-voting
- Aquaculture disease management and microbiota
- Neuroblastoma Research and Treatments
- Advanced Steganography and Watermarking Techniques
- Biochemical and Molecular Research
- Toxoplasma gondii Research Studies
- Vector-borne infectious diseases
- Cancer therapeutics and mechanisms
Wellcome/MRC Institute of Metabolic Science
2016-2024
University of Cambridge
2016-2024
Wellcome Trust
2016-2024
Medical Research Council
2016-2024
AstraZeneca (United Kingdom)
2022-2024
National Institute of Technology Hamirpur
2020
Central Drug Research Institute
2013-2018
Cell and organelle membranes consist of a complex mixture phospholipids (PLs) that determine their size, shape, function. Phosphatidylcholine (PC) is the most abundant phospholipid in eukaryotic membranes, yet how cells sense regulate its levels vivo remains unclear. Here we show PCYT1A, rate-limiting enzyme PC synthesis, intranuclear re-locates to nuclear membrane response need for PL synthesis yeast, fly, mammalian cells. By aligning imaging with lipidomic analysis data-driven modeling,...
Perilipins (PLINs) play a key role in energy storage by orchestrating the activity of lipases on surface lipid droplets. Failure this results severe metabolic disease humans. Unlike all other droplet-associated proteins, PLINs localize almost exclusively to phospholipid monolayer surrounding droplet. To understand how they sense and associate with unique topology droplet surface, we studied localization human inSaccharomyces cerevisiae,demonstrating that targeting mechanism is highly...
The glycine to cysteine mutation at codon 12 of Kirsten rat sarcoma (KRAS) represents an Achilles heel that has now rendered this important GTPase druggable. Herein, we report our structure-based drug design approach led the identification 14, AZD4747, a clinical development candidate for treatment KRASG12C-positive tumors, including central nervous system (CNS) metastases. Building on earlier discovery C5-tethered quinazoline AZD4625, excision usually critical pyrimidine ring yielded weak...
Obesity in humans and mice is associated with elevated levels of two hormones responsive to cellular stress, namely GDF15 FGF21. Over-expression each these weight loss beneficial metabolic changes but where they are secreted from what required for physiologically the context overfeeding remains unclear. Here we used tissue selective knockout mouse models human transcriptomics determine source circulating obesity. We then generated characterized phenotypes GDF15/FGF21 double mice. Circulating...
Apicomplexan protists such as Plasmodium and Toxoplasma contain a mitochondrion relic plastid (apicoplast) that are sites of protein translation. Although there is emerging interest in the partitioning function translation factors participate apicoplast mitochondrial peptide synthesis, composition organellar ribosomes remains to be elucidated. We carried out an analysis complement core ribosomal subunits encoded by either parasite or nuclear genomes, accompanied survey ribosome assembly for...
India is world's largest democracy and the essence of any lies in fact that people choose their own representatives. But present era, fair election process facing a lot problems like booth capturing, rigging, fake voting, tampering with Electronic Voting Machines (EVMs) etc. Being responsible engineers, it's our duty to do something curb this menace. In commonly used EVMs, voting takes place electronically eliminates use ballot paper cast votes elections as it very time consuming errors...
Bfl-1, a member of the Bcl-2 family proteins, plays crucial role in apoptosis regulation and has been implicated cancer cell survival resistance to venetoclax therapy. Due unique cysteine residue BH3 binding site, development covalent inhibitors targeting Bfl-1 represents promising strategy for treatment. Herein, optimization cellular tool from lead-like hit using structure based design is described. Informed by reversible X-ray fragment screen, establish interactions with key glutamic acid...
Covalent inhibition is a valuable modality in drug discovery because of its potential ability decoupling pharmacokinetics from pharmacodynamics by prolonging the residence time on target interest. This increase occupancy limited only rate turnover. However, limitation such studies to translate vitro assessment appropriate cellulo engagement parameter covalent probes. Estimation parameters often impeded low-throughput nature current probe-free approaches. In this study, an ultra-performance...
Mitochondrial dysfunction has been reported in obesity and insulin resistance, but primary genetic mitochondrial is generally not associated with these, arguing against a straightforward causal relationship. A rare exception, recently identified humans, syndrome of lower body adipose loss, leptin-deficient severe upper overgrowth, resistance caused by the p.Arg707Trp mutation MFN2 , encoding mitofusin 2. How resulting selective form leads to tissue- depot-specific growth abnormalities...
The malaria parasite Plasmodium falciparum has two translationally active organelles - the apicoplast and mitochondrion, which import nuclear-encoded translation factors to mediate protein synthesis. Initiation of is a complex step wherein initiation (IFs) act in regulated manner form an complex. We identified putative organellar IFs investigated targeting, structure function IF1, IF2 IF3 homologues encoded by nuclear genome. A single PfIF1 targeted apicoplast. Apart from its critical...
Adipogenin (Adig) is an adipocyte-enriched transmembrane protein. Its expression induced during adipogenesis in rodent cells, and a recent genome-wide association study associated body mass index (BMI)-adjusted leptin levels with the ADIG locus. In order to begin understand biological function of Adig, we studied Adig-deficient cultured adipocytes phenotyped Adig null (Adig−/−) mice. Data from cells suggest that required for adipogenesis. vivo, Adig−/− mice are leaner than wild-type when fed...
Ribosome assembly is critical for translation and regulating the response to cellular events requires a complex interplay of ribosomal RNA proteins with factors. We investigated putative participants in biogenesis reduced organellar ribosomes Plasmodium falciparum identified homologues two GTPases - EngA Obg that were found mitochondria. Both are indispensable bacteria P. berghei among 'essential' parasite blood stage recently. PfEngA PfObg1 interacted mitoribosomes vivo. GTP stimulated...
Summary Obesity in mice and humans is associated with elevated levels of at least two hormones responsive to cellular stress, namely GDF15 FGF21. Over-expression each these weight loss beneficial metabolic changes but where they are secreted from what required for physiologically the context overfeeding remains unclear. Here we used tissue selective knockout mouse models establish that, like FGF21, circulating primarily derived liver, rather than adipose tissue, muscle or macrophages high...
A biallelic missense mutation in mitofusin 2 (MFN2) causes multiple symmetric lipomatosis and partial lipodystrophy, implicating disruption of mitochondrial fusion or interaction with other organelles adipocyte differentiation, growth and/or survival. In this study, we aimed to document the impact loss 1 (Mfn1) (Mfn2) on adipogenesis cultured cells.
Abstract Objective A biallelic missense mutation in mitofusin 2 ( MFN2 ) causes multiple symmetric lipomatosis and partial lipodystrophy, implicating disruption of mitochondrial fusion or interaction with other organelles adipocyte differentiation, growth and/or survival. In this study, we aimed to document the impact loss 1 Mfn1 Mfn2) on adipogenesis cultured cells. Methods We characterised differentiation wildtype (WT), -/- Mfn2 mouse embryonic fibroblasts (MEFs) 3T3-L1 preadipocytes which...
Abstract Mitochondrial dysfunction has been reported in obesity and insulin resistance, but primary genetic mitochondrial is generally not associated with these, arguing against a straightforward causal relationship. A rare exception, recently identified humans, syndrome of lower body adipose loss, leptin-deficient severe upper overgrowth, resistance caused by the p.Arg707Trp mutation MFN2 , encoding mitofusin-2. How this selective perturbation function leads to tissue- depot-specific growth...