A5014709451- RNA modifications and cancer
- Cancer-related gene regulation
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- Bioinformatics and Genomic Networks
- Genetic Associations and Epidemiology
- Hemophilia Treatment and Research
- Ubiquitin and proteasome pathways
- Platelet Disorders and Treatments
- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- Adipokines, Inflammation, and Metabolic Diseases
- Receptor Mechanisms and Signaling
- Diabetes and associated disorders
- Genomics and Phylogenetic Studies
- Gene expression and cancer classification
- Blood Coagulation and Thrombosis Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Genomics and Chromatin Dynamics
- Metabolism, Diabetes, and Cancer
- Liver Disease Diagnosis and Treatment
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Regulation of Appetite and Obesity
- Asthma and respiratory diseases
Indian Institute of Science Education and Research, Tirupati
2019-2024
MRC Laboratory of Molecular Biology
2011-2024
Medical Research Council
2014-2016
Council for Scientific and Industrial Research
2012
University of Cambridge
2012
Institute of Genomics and Integrative Biology
2004-2011
Council of Scientific and Industrial Research
2005-2011
University of Gothenburg
2009-2011
Natural genetic variation in the human genome is a cause of individual differences responses to medications and an underappreciated burden on public health. Although 108 G-protein-coupled receptors (GPCRs) are targets 475 (∼34%) Food Drug Administration (FDA)-approved drugs account for global sales volume over 180 billion US dollars annually, prevalence among GPCRs targeted by unknown. By analyzing data from 68,496 individuals, we find that show within functional regions such as drug-...
OBJECTIVE Common variants in PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 genes have been shown to be associated with type 2 diabetes European populations by genome-wide association studies. We studied the of common these eight related traits Indians combining data from two independent case–control RESEARCH DESIGN AND METHODS genotyped single nucleotide polymorphisms (PPARG-rs1801282, KCNJ11-rs5219, TCF7L2-rs7903146, SLC30A8-rs13266634, HHEX-rs1111875, CDKN2A-rs10811661,...
Background Previous studies of network properties human disease genes have mainly focused on monogenic diseases or cancers and suffered from discovery bias. Here we investigated the complex identified by genome-wide association (GWAs), thereby eliminating Principal findings We derived a (n = 54) 349) to explore shared genetic architecture diseases. evaluated centrality measures in comparison with essential interactome. The showed that belonging same class do not always share common genes. A...
Excessive expansions of glutamine (Q)-rich repeats in various human proteins are known to result severe neurodegenerative disorders such as Huntington's disease and several ataxias. However, the physiological role these consequences more moderate repeat variation remain unknown. Here, we demonstrate that Q-rich domains highly enriched eukaryotic transcription factors where they act functional modulators. Incremental changes number yeast transcriptional regulator Ssn6 (Cyc8) systematic,...
The control over the extent and timing of G protein signaling is provided by regulator (RGS) proteins that deactivate α subunits (Gα). Mammalian genomes encode 20 canonical RGS 16 Gα genes with key roles in physiology disease. To understand principles governing selectivity regulation RGS, we examine catalytic activity all human their for a complete set substrates using real-time kinetic measurements living cells. data reveal rules RGS-Gα recognition, structural basis its selectivity, provide...
The ability of a gene to cause disease is known be associated with the topological position its protein product in molecular interaction network. Pleiotropy, human genetic diseases, refers different mutations within same pathological effects. Here, we hypothesized that genes pleiotropic effects would their network properties.Shared genes, effects, were more central than specific one disease, Furthermore, shared phenotypically divergent diseases (phenodiv genes) those similar diseases. Shared...
Abstract Numerical centrosome aberrations underlie certain developmental abnormalities and may promote cancer. A cell maintains normal numbers by coupling duplication with segregation, which is achieved through sustained association of each a mitotic spindle pole. Although the microcephaly- primordial dwarfism-linked centrosomal protein CEP215 has been implicated in this process, molecular mechanism responsible remains unclear. Here, using proteomic profiling, we identify minus end-directed...
The proteasome has pronounced preferences for the amino acid sequence of its substrates at site where it initiates degradation. Here, we report that modulating these sequences can tune steady-state abundance proteins over 2 orders magnitude in cells. This is same dynamic range as seen inducing ubiquitination through a classic N-end rule degron. stability and His3 constructs dictated by initiation affect survival yeast cells show variation proteasomal fitness. proteasome's are linked directly...
Elevated high-sensitivity C-reactive protein (hsCRP) levels have frequently been shown to be associated with type 2 diabetes (T2D); however, very little is known about this in Asian Indians, a high-risk group.The aim of the study was assess association hsCRP T2D and determine its correlates North Indians Indo-European origin.A cross-sectional population-based 2520 urban subjects, comprising 1410 patients 1110 nondiabetic carried out 18 metabolic traits were assessed.Median significantly...
Complex diseases are associated with altered interactions between thousands of genes. We developed a novel method to identify and prioritize disease genes, which was generally applicable complex diseases. identified modules highly interconnected genes in disease-specific networks derived from integrating gene-expression protein interaction data. examined if those were enriched for disease-associated SNPs, could be used find functional studies. First, we analyzed publicly available gene...
Achieving functional specificity while minimizing cost to fitness is a key constraint during evolution. Formation of biological condensates by liquid–liquid phase separation (LLPS) appears serve as an important regulatory mechanism generate moderate in molecular recognition maintaining reasonable for terms design complexity. serves unique achieving some level without huge fitness. Rapid formation vivo induced specific cellular or environmental triggers has been shown be increasing Here we...
Emerging evidence suggests that amino acid homorepeats (HRs) in proteins (HRPs) contribute to protein interactability. What is the role of HRs human-pathogen interactions? We find pathogens engage physiologically important human HRPs, thereby affecting diverse host physiological processes. From pathogen standpoint, (i) eukaryotic more HRPs but with host-sparse HRs, leading disparate and discriminate interactions, (ii) prokaryotic less host-abundant non-polar via proxies bringing about or...
Summary Rice, a staple cereal crop, faces significant threats from rising temperatures, affecting all growth stages including early seedling establishment. Despite being critical in determining overall and productivity, response to heat stress during the stage remains understudied. This research aimed assess impact of acute on rice seedlings unravel underlying molecular mechanisms. Rice were exposed varying intensities durations determine threshold growth. To elucidate transcription factor...
MicroRNAs (miRNAs) play a key role in regulating mRNA expression, and individual miRNAs have been proposed as diagnostic therapeutic candidates. The identification of such candidates is complicated by the involvement multiple mRNAs well unknown disease topology miRNAs. Here, we investigated if disease-associated regulate modules mRNAs, those act complementarily or synergistically, single combinations can be targeted to alter module functions. We first analyzed publicly available miRNA...
Abstract TATA-box binding protein (TBP) is required for every single transcription event in archaea and eukaryotes. It binds DNA harbors two repeats with an internal structural symmetry that show sequence asymmetry. At various times evolution, TBP has acquired multiple interaction partners different organisms have evolved paralogs additional regions. Together, these observations raise questions of what molecular determinants (i.e. key residues) led to the ability acquire new interactions,...