A5035866336- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- Reproductive Biology and Fertility
- Machine Learning in Materials Science
- RNA Research and Splicing
- Advanced Graph Neural Networks
- Chromosomal and Genetic Variations
- Computational Drug Discovery Methods
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Diabetes and associated disorders
- Cellular Mechanics and Interactions
- MicroRNA in disease regulation
- Pancreatic function and diabetes
- Breast Cancer Treatment Studies
- Topic Modeling
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Prenatal Screening and Diagnostics
- Cancer Cells and Metastasis
- Mesenchymal stem cell research
- Single-cell and spatial transcriptomics
- Acute Kidney Injury Research
- Hypothalamic control of reproductive hormones
University of Oxford
2015-2025
Humboldt-Universität zu Berlin
2025
Karunya University
2023
DeepMind (United Kingdom)
2020-2021
Google (United States)
2020-2021
University College London
2018
Moorfields Eye Hospital
2018
Cornell University
2018
Imperial College London
2005-2013
University of Massachusetts Chan Medical School
2013
The ribonuclease III enzyme Dicer is essential for the processing of micro-RNAs (miRNAs) and small interfering RNAs (siRNAs) from double-stranded RNA precursors. miRNAs siRNAs regulate chromatin structure, gene transcription, mRNA stability, translation in a wide range organisms. To provide model system to explore role Dicer-generated differentiation mammalian cells vivo, we have generated conditional allele. Deletion at an early stage T cell development compromised survival αβ lineage...
Human clinical trials in type 1 diabetes (T1D) patients using mesenchymal stem cells (MSC) are presently underway without prior validation a mouse model for the disease. In response to this void, we characterized bone marrow-derived murine MSC their ability modulate immune responses context of T1D, as represented NOD mice. comparison mice, BALB/c-MSC mice were found express higher levels negative costimulatory molecule PD-L1 and promote shift toward Th2-like treated addition, transfer from...
Renal ischemia reperfusion injury (IRI) is associated with significant morbidity and mortality. Given the importance of microRNAs (miRNAs) in regulating gene expression, we examined expression profiles miRNAs following renal IRI. Global miRNA profiling on samples prepared from kidneys C57BL/6 mice that underwent unilateral warm revealed nine (miR-21, miR-20a, miR-146a, miR-199a-3p, miR-214, miR-192, miR-187, miR-805, miR-194) are differentially expressed IRI when compared sham controls....
Here we present a machine learning framework and model implementation that can learn to simulate wide variety of challenging physical domains, involving fluids, rigid solids, deformable materials interacting with one another. Our framework---which term "Graph Network-based Simulators" (GNS)---represents the state system particles, expressed as nodes in graph, computes dynamics via learned message-passing. results show our generalize from single-timestep predictions thousands particles during...
During female meiosis, bivalent chromosomes are thought to be held together from birth until ovulation by sister chromatid cohesion mediated cohesin complexes whose ring structure depends on kleisin subunits, either Rec8 or Scc1. Because is established at DNA replication in the embryo, its maintenance for such a long time may require turnover. To address whether Rec8- Scc1-containing holds bivalents and it turns over, we created mice subunits can cleaved TEV protease. We show microinjection...
Introduction Standards for Reporting of Diagnostic Accuracy Study (STARD) was developed to improve the completeness and transparency reporting in studies investigating diagnostic test accuracy. However, its current form, STARD 2015 does not address issues challenges raised by artificial intelligence (AI)-centred interventions. As such, we propose an AI-specific version checklist (STARD-AI), which focuses on AI accuracy studies. This paper describes methods that will be used develop STARD-AI....
The mammalian heart is derived from multiple cell lineages; however, our understanding of when and how the diverse cardiac types arise limited. We mapped origin embryonic mouse at single-cell resolution using a combination transcriptomic, imaging, genetic lineage labeling approaches. This mapping provided transcriptional anatomic definition progenitor types. Furthermore, it revealed pool that anatomically transcriptionally distinct currently known progenitors. Besides contributing to...
Graph neural networks (GNN) have shown promising results for several domains such as materials science, chemistry, and the social sciences. GNN models often contain millions of parameters, like other network (NN) models, are fed only a fraction graphs that make up training dataset in batches to update model parameters. The effect batching algorithms on time performance has been thoroughly explored NNs but not yet GNNs. We analyze two different graph based namely static dynamic batching. use...
It is generally assumed that the inhibitory neurotransmitter GABA and stimulatory glutamate are released from different neurons in adults. However, this tenet has made it difficult to explain how same afferent signals can cause opposite changes release. Such reciprocal release a central mechanism neural control of many physiological processes including activation gonadotropin-releasing hormone (GnRH) neurons, signal for ovulation. Activation GnRH requires simultaneous suppression stimulation...
X chromosome inactivation involves multiple levels of chromatin modification, established progressively and in a stepwise manner during early development. The chromosomal protein Smchd1 was recently shown to play an important role DNA methylation CpG islands (CGIs), late step the pathway that is required for long-term maintenance gene silencing. Here we show inactive (Xi) CGI can occur via either Smchd1-dependent or -independent pathways. methylation, primary pathway, acquired gradually over...
The specification of a subset epiblast cells to acquire neural fate constitutes the first step in generation nervous system. Little is known about signals required for induction mouse. We have analysed role BMP signalling this process. demonstrate that prior gastrulation, Bmp2/4 via Bmpr1a maintains pluripotency and prevents precocious differentiation tissue, at least part by maintaining Nodal signalling. find during BMPs 60A subgroup cooperate with maintain pluripotency. inhibition...
A number of clinical trials are underway to test whether mesenchymal stem cells (MSCs) effective in treating various diseases, including type 1 diabetes. Although this cell therapy holds great promise, the optimal source MSCs has yet be determined with respect major histocompatibility complex matching. Here, we examine question by testing ability congenic MSCs, obtained from NOR mouse strain, reverse recent-onset diabetes NOD mice, as well determine immunomodulatory effects vivo.NOR were...
Activation of the egg by sperm is first, vital stage embryogenesis. The protein PLCζ has been proposed as physiological agent that triggers Ca2+ oscillations normally initiate Consistent with this, recombinant induces in eggs and debilitating mutations PLCZ1 gene are associated infertility men. However, there no evidence knockout encoding abolishes ability to induce eggs. Here, we show derived from Plcz1-/- male mice fail trigger eggs, cause polyspermy thus demonstrate these oscillations....
Abstract T cell activation requires signaling through the TCR and costimulatory molecules, such as CD28. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression posttranscriptionally also known to be involved in lymphocyte development function. In this paper, we set out examine potential roles of miRNAs activation, using genome-wide profiling identify differentially regulated following activation. One upregulated after miR-214, was predicted capable targeting Pten based on...
The nuclear matrix protein Cip1-interacting zinc finger 1 (CIZ1) promotes DNA replication in association with cyclins and has been linked to adult pediatric cancers. Here we show that CIZ1 is highly enriched on the inactive X chromosome (Xi) mouse human female cells retained by interaction RNA-dependent matrix. recruited Xi response expression of inactive-specific transcript (Xist) RNA during earliest stages inactivation embryonic stem dependent C-terminal anchor domain E repeats Xist ....
Sister chromatid cohesion mediated by the cohesin complex is essential for chromosome segregation in mitosis and meiosis [1]. Rec8-containing cohesin, bound to Smc3/Smc1α or Smc3/Smc1β, maintains bivalent mammalian [2-6]. In females, meiotic DNA replication recombination occur fetal oocytes. After birth, oocytes arrest at prolonged dictyate stage until recruited grow into mature that divide ovulation. How maintained arrested remains a pivotal question relevant maternal age-related...
The inactive X chromosome (Xi) in female mammals adopts an atypical higher-order chromatin structure, manifested as a global loss of local topologically associated domains (TADs), A/B compartments and formation two mega-domains. Here we demonstrate that the non-canonical SMC family protein, SmcHD1, which is important for gene silencing on Xi, contributes to this unique architecture. Specifically, allelic mapping transcriptome epigenome SmcHD1 mutant cells reveals appearance sub-megabase...
The Smchd1 gene encodes a large protein with homology to the SMC family of proteins involved in chromosome condensation and cohesion. Previous studies have found that has an important role CpG island (CGI) methylation on inactive X (Xi) stable silencing some Xi genes. In this study, using genome-wide expression analysis, we showed is required for around 10% genes Xi, apparently independent CGI hypomethylation, and, moreover, these nonrandomly occur clusters. Additionally, at cluster four...
The Polycomb repressive complexes PRC1 and PRC2 are key mediators of heritable gene silencing in multicellular organisms. Here we characterise AEBP2, a known cofactor which, vitro, has been shown to stimulate activity. We show that AEBP2 localises specifically target loci, including the inactive X chromosome. Proteomic analysis confirms associates exclusively with complexes. However, embryos homozygous for targeted mutation Aebp2 unexpectedly revealed Trithorax phenotype, normally linked...
Abstract During embryogenesis, endothelial cells (ECs) are generally described to arise from a common pool of progenitors termed angioblasts, which diversify through iterative steps differentiation form functionally distinct subtypes ECs. A key example is the formation lymphatic ECs (LECs), thought largely transdifferentiation venous endothelium. Opposing this model, here we show that initial expansion mammalian LECs primarily driven by in situ mesenchymal and does not require transition an...
The anterior visceral endoderm (AVE) differs from the surrounding (VE) in its migratory behavior and ability to restrict primitive streak formation opposite side of mouse embryo. To characterize molecular bases for unique properties AVE, we combined single-cell RNA sequencing VE prior during AVE migration with phosphoproteomics, high-resolution live-imaging, short-term lineage labeling intervention. This identified transient nature attenuation "anteriorizing" gene expression as cells migrate...