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Principles of human development and germ cell program
<p>Specification of human primordial germ cells (hPGCs) occurs around gastrulation, a critical juncture when the specification of the primary somatic lineages also occurs. In combination with human preimplantation embryos, in<em> vitro</em> models and hPGCs from aborted fetuses, our objective is to elucidate the origin and properties of the early human germline.</p> <p>For the mec… more
Infection, Immunity and Inflammation
Mathematical genomics and medicine
Value in people award.
Training Health Researchers into Vocational Excellence in East Africa
1. Develop and sustain a consortium functioning as a strong network by: i. Exchange of staff ii. Developing collaborative research projects iii. Regular communication between consortium members iv. Adjunct appointments of senior research scientists v. Joint academic programmes attended by trainees from THRiVE vi. Joint annual meetings vii. Joint supervision of PhD students 2. Empower institutions… more
PhD Training Programme for Clinicians at the University of Cambridge.
The generation of induced pluripotent stem cells from somatic cells brings the possibility of translational applications in regenerative medicine, disease modelling and drug screening a step closer. However current derivation methods remain inefficient, unpredictable and clinically unsafe. In order to maximise the translational potential of iPS cells in clinical medicine, these methods must be op… more
PhD Training Programme for Clinicians at the University of Cambridge: 'Neural and molecular mechanisms involved in human obesity'.
Body mass is highly heritable and a number of genes have been identified, in which mutations lead to severe early onset obesity. The aim of my research is to investigate the molecular mechanisms involved in mediating the effects of the adipocyte derived hormone leptin on fertility through the study of naturally occurring mutations in the leptin receptor. I will also investigate the functional eff… more
PhD Training Programme for Clinicians at the University of Cambridge: a post-genomic study of inflammatory bowel disease.
The project is integrating clinical and laboratory data to examine, using microarrays, whether gene expression signatures in subsets of peripheral blood mononuclear cells from patients with inflammatory bowel disease can be correlated with disease behaviour both in terms of disease course, including relapse rate, and treatment response. A correlation has been identified in other diseases (e.g. sm… more
The role of Myosin VI in Membrane traffic and Cell Division.
Myosin motor proteins move membrane and vesicles along actin tracks. Myosin VI unlike almost all other myosins moves towards the minus end of actin filaments. Our intracellular localisation of myosin VI at the Golgi complex, in clathrin coated pits/vesicles and at kinetochores in mitotic cells indicates that it functions in a wide variety of intracellular processes. The diverse roles of myosin VI… more
21st Century Families: Parent-child relationships and children's psychological wellbeing
<p>New pathways to parenthood have recently emerged that did not exist, nor had even been imagined, at the turn of the 21<sup>st</sup> century. Individuals who were previously unknown to each other have begun to meet over the internet with the purpose of having children together; transgender men and women have begun to have children through medically assisted reproduction; single heterosexual men… more
From Cures to Courts of Justice: The Medical Encounter and Social Order in Early Modern Spain
<p>Early modern encounters have mainly been studied as transactions between individual sick people and their healers. This project shifts the focus by placing encounters within the communities that structured early modern lives and the practices and expectations of social order that shaped them. The variety of encounters that took place in the Catholic kingdom of Castile provides an ideal case st… more
Applying causal interventions to brain networks underlying adaptive perceptual decision making.
<p>The contribution of individual brain regions to perception is not static, and is determined both by task experience and particular stimulus demands. To investigate these dynamic contributions, I propose to use non-invasive brain stimulation combined with electrophysiological measurements. This combination will provide a window into the dynamics of causal relationships between behaviour and spe… more
Genetic and functional interactions in the mammalian DNA-damage response
<p>DNA in our cells is frequently subject to a wide array of molecularly-distinct forms of damage. To cope with this, life has evolved multiple DNA repair and associated processes, collectively termed the DNA-damage response (DDR). While considerable progress has been made in identifying DDR proteins and their regulators, much remains to be learned about how they operate and are controlled. Build… more
The cognitive neuroscience of over-eating: normative and clinical studies of goal-driven and stimulus-driven responses
<p>There is a pressing need to understand the phenotypic variations of obesity in order to elucidate the diverse pathways and mechanisms by which it arises and, ultimately, to offer suitably tailored interventions. My proposed work aims to provide insights into the cognitive neuroscience of health-harming over-consumption. Its ultimate goals are to characterise cognitive mechanisms underlyi… more
Putting genomic surveillance at the heart of viral epidemic response.
<p>This proposal is to develop an end-to-end system for processing samples from viral outbreaks to generate real-time epidemiological information that is interpretable and actionable by public health bodies. Fast evolving RNA viruses (such as Ebola, MERS, SARS, influenza etc) continually accumulate changes in their genomes that can be used to reconstruct the epidemiological processes that dr… more
Understanding mammalian interphase genome structure in mouse ES cells
<p>The folding of genomic DNA from the beads-on-a-string like structure of nucleosomes into higher order assemblies is critically linked to nuclear processes, but it is unclear to what degree it is a cause or consequence of function. We aim to understand whether the Nucleosome Remodeling and Deacetylation (NuRD) complex regulates chromatin structure to control transcription, or whether it is NuRD… more
Molecular mechanisms controlling germline stem cell biology
<p>The ability of stem cells to replenish and differentiate is critical for tissue growth, repair, and homeostasis. Yet, our understanding of the molecular mechanisms governing stem cell fate transitions remains limited. Through a systematic RNAi screen using the Drosophila germline as a model for stem cell biology, I uncovered a central role for ribosome biogenesis and protein synthesis regulati… more
Intestinal epithelial cells: at the interface of the microbiota and mucosal immunity
<p>Intestinal infections affect billions of people worldwide, resulting in nearly 1.4 million deaths each year. The commensal microbiota can prevent pathogenic infection, as demonstrated by increased susceptibility to infection upon antibiotic use; however, the precise mechanisms of microbiota-mediated protection are not well-characterized. I have recently discovered that colonization of mice wit… more