A5081867406- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Gene Regulatory Network Analysis
- Bacterial Genetics and Biotechnology
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Single-cell and spatial transcriptomics
- Enzyme Structure and Function
- Developmental Biology and Gene Regulation
- Genomics and Phylogenetic Studies
- Bioinformatics and Genomic Networks
- Prion Diseases and Protein Misfolding
- Pluripotent Stem Cells Research
- Photosynthetic Processes and Mechanisms
- CRISPR and Genetic Engineering
- Helicobacter pylori-related gastroenterology studies
- Microbial Metabolic Engineering and Bioproduction
- Computational Drug Discovery Methods
- Microbial Community Ecology and Physiology
- Epigenetics and DNA Methylation
- Veterinary medicine and infectious diseases
- Gene expression and cancer classification
- Mass Spectrometry Techniques and Applications
National University Cancer Institute, Singapore
2018-2023
National University of Singapore
2018-2023
University of Luxembourg
2006-2021
Universidad de Zaragoza
2007-2016
Consejo Superior de Investigaciones Científicas
2013-2014
Instituto de Química Física Blas Cabrera
2010
Universidad Nacional Autónoma de México
2008
Great efforts are being devoted to get a deeper understanding of disease-related dysregulations, which is central for introducing novel and more effective therapeutics in the clinics. However, most human diseases highly multifactorial at molecular level, involving dysregulation multiple genes interactions gene regulatory networks. This issue hinders elucidation disease mechanism, including identification disease-causing interactions. Most current network-based approaches study mechanisms do...
Abstract Background Prion proteins conform a special class among amyloids due to their ability transmit aggregative folds. Prions are known act as infectious agents in neurodegenerative diseases animals, or key elements transcription and translation processes yeast. It has been suggested that prions contain specific sequential domains with distinctive amino acid composition physicochemical properties allow them control the switch between soluble β -sheet aggregated states. Those...
The increasing antibiotic resistance evolved by Helicobacter pylori has alarmingly reduced the eradication rates of first-line therapies. To overcome current circulating resistome, we selected a novel potential therapeutic target in order to identify new candidate drugs for treating H. infection. We screened 1120 FDA-approved molecules that bind essential response regulator HsrA and potentially inhibit its biological function. Seven natural flavonoids were identified as binders. All these...
The R dx A oxygen‐insensitive nitroreductase of the human gastric pathogen H elicobacter pylori is responsible for susceptibility this organism to redox active prodrug metronidazole [2‐(2‐methyl‐5‐nitro‐1 ‐imidazol‐1‐yl)ethanol]. Loss‐of‐function mutations in rdxA are primarily resistance therapeutic. exhibits potent NADPH oxidase activity under aerobic conditions and reductase strictly anaerobic conditions. In present study, we report crystal structure , which a homodimer exhibiting domain...
The stochastic dynamics and regulatory mechanisms that govern differentiation of individual human neural precursor cells (NPC) into mature neurons are currently not fully understood. Here, we used single-cell RNA-sequencing (scRNA-seq) developing to dissect/identify NPC subtypes critical developmental stages alternative lineage specifications. This study comprises an unsupervised, high-resolution strategy for identifying cell bifurcations, tracking the transcript kinetics subpopulations,...
In the filamentous cyanobacterium Anabaena sp. PCC 7120, ferric uptake regulator FurA functions as a global transcriptional regulator. Despite several analyses have focused on elucidating FurA-regulatory network, number of target genes described for this essential transcription factor is limited to handful examples. article, we combine an in silico genome-wide predictive approach with experimental determinations better define regulon. Predicted FurA-binding sites were identified upstream 215...
Prions are a particular type of amyloids related to large variety important processes in cells, but also responsible for serious diseases mammals and humans. The number experimentally characterized prions is still low corresponds handful examples microorganisms mammals. Prion aggregation mediated by specific protein domains with remarkable compositional bias towards glutamine/asparagine against charged residues prolines. These features have been used predict new prion proteins the genomes...
The specific recognition of genomic cis-regulatory elements by transcription factors (TFs) plays an essential role in the regulation coordinated gene expression. Studying mechanisms determining binding specificity protein-DNA interactions is thus important goal. Most current approaches for modeling TF rely on knowledge large sets cognate target sites and consider only information contained their primary sequence. Here we describe a structure-based methodology predicting sequence motifs...
The RNA polymerase II-associated protein 1 (RPAP1) is conserved across metazoa and required for stem cell differentiation in plants; however, very little known about its mechanism of action or role mammalian cells. Here, we report that RPAP1 essential the expression identity genes viability. Depletion triggers de-differentiation, facilitates reprogramming toward pluripotency, impairs differentiation. Mechanistically, show interaction between II (RNA Pol II) Mediator, as well recruitment...
Stem cell differentiation is a complex biological process. Cellular heterogeneity, such as the co-existence of different subpopulations within population, partly hampers our understanding this The modern single-cell gene expression technologies, RT-PCR and RNA-seq, have enabled us to elucidate heterogeneous subpopulations. However, identification transcriptional regulatory network (TRN) for each subpopulation population genes determining specific fates (lineage specifiers) remains challenge...
Antibiotic resistance is a major cause of the increasing failures in current eradication therapies against Helicobacter pylori. In this scenario, repurposing drugs could be valuable strategy to fast-track novel antimicrobial agents. present study, we analyzed inhibitory capability 1,4-dihydropyridine (DHP) antihypertensive on essential function H. pylori response regulator HsrA and investigated both vitro activities vivo efficacy DHP treatments Six different commercially available highly...
The version 2.0 of Tractor_DB is now accessible at its three international mirrors: Author Webpage, Webpage and Webpage. This database contains a collection computationally predicted Transcription Factors' binding sites in gamma-proteobacterial genomes. These data should aid researchers the design microarray experiments interpretation their results. They also facilitate studies Comparative Genomics regulatory networks this group organisms. In paper we describe main improvements incorporated...
The folding pathway, three-dimensional structure and intrinsic dynamics of proteins are governed by their amino acid sequences. Internal protein surfaces with physicochemical properties appropriate to modulate conformational fluctuations could play important roles in dynamics. We show here that contain buried interfaces high polarity low packing density, coined as LIPs: Light Interfaces Polarity, whose make them unstable. structures well-characterized equilibrium kinetic intermediates...
Familial hypercholesterolemia (FH), a genetic disorder with prevalence of 0.2%, represents high-risk factor to develop cardiovascular and cerebrovascular diseases. The majority most severe FH cases are associated mutations in the receptor for low-density lipoproteins (LDL-r), but molecular basis explaining connection between mutation phenotype is often unknown, which hinders early diagnosis treatment disease. We have used atomistic simulations explore complete SNP mutational space (227...
Specific protein–DNA interactions are central to a wide group of processes in the cell and have been studied both experimentally computationally over years. Despite increasing collection complexes, so far only few studies aimed at dissecting structural characteristics DNA binding among evolutionarily related proteins. Some questions that remain be answered are: (a) what is contribution different readout mechanisms members given superfamily, (b) degree interface similarity superfamily how...
The low‐density lipoprotein receptor ( LDLR ) captures circulating lipoproteins and delivers them in the endosome for degradation. Its function is essential cholesterol homeostasis, mutations are major cause of familiar hypercholesterolemia. release LDL usually attributed to acidification. As pH drops, affinity / complex reduced, whereas strength a self‐complex formed between two domains (i.e. binding domain β‐propeller domain) increases. However, an alternative model states that, as...