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GFP zebrafish

Gene regulatory programmes driving cell fate decisions

Gene regulatory programmes driving cell fate decisions

Most cells within an organism contain identical copies of the genome, but selectively use different portion of their genomes and transcribe different genes. We study the mechanisms underlying changes in gene expression and how they generate the myriad of different cell types and produce organ-specific transcriptional signatures in the human embryo.

Gene expression dynamics in response to cell signalling

We are investigating how gene expression dynamics are harmonised with developmental timing to control cell fate decisions, using the Drosophila embryo as a model. Coupled with this, we are studying how the major bone morphogenetic protein (BMP) signal is transduced intracellularly to induce gene expression changes.

Principal investigator: Professor Hilary Ashe

Mechanisms of transcriptional regulation in development and evolution

We are interested in how specific changes in chromatin accessibility and in transcription factor occupancy instruct cell fate decision during development, and are responsible for the evolution of new anatomical structures. To study this, we use genomics (mainly ChIP-seq, RNA-seq) and genetics approaches directly in vertebrate embryos (mouse, chick and zebrafish).

Principal investigator: Professor Nicoletta Bobola

Analysis of craniofacial development and associated congenital malformations

We delineate the genetic mutations underlying syndromic forms of cleft lip and palate and use developmental genetic techniques to dissect the underlying molecular pathology. In parallel, we are utilising high-throughput techniques, including RNA-seq and ChIP-seq, to delineate the functional organisation of the regulatory genome driving facial development and using this information to determine how genetic changes affect gene regulation in cleft lip and palate.

Principal investigator: Professor Mike Dixon

Genomic regulation of human embryogenesis

We are interested in unravelling how the human post-implantation embryo is assembled, in particular its genomic regulation.

Our aspiration is that by working collaboratively across organ systems we can provide comprehensive insights of great benefit to developmental medicine (e.g. diagnosing damaging genetic variation) and stem cell biology/regenerative medicine by creating a roadmap for stem cell differentiation and optimised factors for cell reprogramming.

Principal investigator: Professor Neil Hanley

Understanding the dynamic nature of cell state transitions in development, cancer and regeneration

We aim to understand how cells make cell state transitions from proliferation to differentiation, or to quiescence and reactivation. Understanding how these transitions are regulated is key to understanding how tissues are built in development, maintained in the adult and repaired or subverted to disease, particularly cancer.

Our working hypothesis is that cell state transitions are not simply driven by genes being on or off, but by a change in the dynamics of gene expression.

We use single cell approaches, absolute quantitation of molecular species (mRNA, microRNAs and protein), live imaging of single cells and tissues, multiple experimental model systems (mouse and human neural stem cells, zebrafish and mouse embryos) and mathematical modelling, in order to understand how changes in gene expression dynamics underlie cell state transitions in neural development.

Principal investigator: Professor Nancy Papalopulu

Transcription factors and breast cancer development

Our goal is to prevent metastatic breast cancer by understanding the molecular basis for the development of specific metastatic phenotypes. Work focuses on the molecular mechanisms that determine changes in gene expression, which subsequently enable disseminated breast cancer cells to colonise specific tissues.

Principal investigator: Dr Paul Shore