The Cellular Genetics Programme explores the consequences of genome variation on human cell biology, and thus gene function in health and disease. We conduct large-scale systematic screens to discover the impact of naturally-occurring and engineered genome mutations in human iPS cells, their differentiated derivatives, and other cell types.
The Cellular Genetics Programme will:
use induced pluripotential stem cells obtained from 100s of people, healthy and with known genetic diseases, differentiated into macrophages, hepatocytes and pancreatic cells to explore the impact, at the cellular level, of naturally occurring common and rare human variation on:
host-pathogen interactions and innate immune responses
integrate results from cellular genetics studies with functional genomics data sets and novel algorithms, to study mechanisms of gene regulation and assist the interpretation of disease variation
create a full reference map of the epigenome and transcriptome of every cell type in the human body using single-cell techniques
further develop CRISPR-Cas technology to perform genome-wide screens of protein coding genes, lnc RNAs and other genome elements in libraries of cells to explore the genomic components influencing a range of cellular phenotypes.
develop and enhance innovative methods for analysis of data from single-cell studies
The Cellular Genetics Programme investigates cell biology and human disease in the fields of infection, innate immunity and metabolism by focusing on cell types implicated in these processes, including the macrophage, the hepatocyte and the pancreatic beta cell.
We are also starting a project that seeks to create a comprehensive reference map of the type and properties of all human cells, the fundamental unit of life, as a basis for understanding, diagnosing, monitoring and treating health and disease.
The International Human Cell Atlas initiative aims to create comprehensive reference maps of all human cells—the fundamental units of life—as a basis for both understanding human health and diagnosing, monitoring, and treating disease.
SC3 is a method for unsupervised clustering of single-cell RNA-seq data. In addition to a graphical user-interface, SC3 provides additional information about potential outliers and marker genes for each cluster.
We have been granted a strategic award from the Wellcome Trust 'The Homunculus in our Thymus: A Cellular Genomics Approach' that enables us to investigate how thymic epithelial cells (TEC) - irrespective of their cell identity - remarkably can express virtually the complete set of protein-coding genes. These studies are relevant to better understand the fundamental function of the immune system and to identify causes of autoimmune diseases.
The Bradley laboratory is a multi-disciplinary environment with a number of parallel research themes. One of our core disciplines is the development and use of genetic technologies which we primarily apply to the mouse genome, although we also embrace studies in other mammalian genomes.
Gene expression involves the transformation of genetic information encoded in DNA sequence into a gene product, such as a protein. Regulation of gene expression is a fundamentally important process in biology because controlling the timing, location and level of gene expression is critical for the gene product to function correctly. The majority of mutations that alter disease risk for most common diseases are thought affect gene regulation, although how these mutations actually function is not well understood in most cases. Our group uses a combination of statistical and experimental approaches to map mutations that affect gene regulation in humans.
The Hemberg group is interested in developing quantitative models of gene expression. Our approach is theoretical and we strive to develop novel mathematical models as well as computational tools that can be used by other researchers.
We use various approaches including genetics, genomics and cell biology to study gene functions in normal development and disease such as cancer. We are particularly interested in stem cell self-renewal, differentiation, and lineage choice.
We measure, model, and modulate cell state. We use genome engineering and synthetic biology to create cell lines that can be employed for CRISPR/Cas9-based genetic screening and high throughput cell biology assays. We develop probabilistic models as well as software tools to accurately analyse the readouts.
The group seeks to elucidate the principles of protein structure evolution, higher order protein structure and protein folding, and the principles underlying protein complex formation and organization. We have a longstanding interest in understanding gene expression regulation, and in our wetlab at the Sanger Institute use mouse T helper cells as a model of cell differentiation.
We aim to learn why being obese causes metabolic and cardiovascular problems and to provide the rational for mechanistically driven therapeutic approaches to prevent these complications which are the meain cause of morbidity among obese patients.
We explore the vast cellular diversity in the human body to: (i) create single-cell level 3D maps of human organs using large-scale spatial transcriptomics and (ii) uncover the specialized functions of brain cell types using large-scale in vitro screens and mouse models. We have a particular focus on studying neural cell type diversity in the human cerebral cortex.