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Search results (Displaying 44 grants)

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Earliest award date
24 Jan 2017
Latest award date
28 Nov 2017
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Principles of human development and germ cell program
<p>Specification of human primordial germ cells (hPGCs)&nbsp;occurs around gastrulation, a critical juncture when the specification of the primary somatic lineages&nbsp;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&nbsp;the mec… more
Amount: £2,750,000
Amount: £2,750,000
Amount: £2,610,000
Amount: £2,490,000
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
Amount: £1,552,401
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
Amount: £147,847
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
Amount: £250,000
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
Amount: £1,636,331
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.&nbsp; Its ultimate goals are to characterise cognitive mechanisms underlyi… more
Amount: £1,500,053
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&nbsp;Ebola, MERS, SARS, influenza etc) continually accumulate changes in their genomes that can be used to reconstruct the epidemiological processes that dr… more
Amount: £482,639
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
Amount: £2,031,409
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
Amount: £1,138,543
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
Amount: £1,212,214
Regulation of nuclear envelope function and links with disease
<p>The nuclear envelope (NE) lies at the interface between the nucleus and the cytoskeleton. It forms a complex structure controlling cell compartmentalization and regulates many processes including nucleo-cytoplasmic transport of proteins and RNA, chromatin organization, DNA replication and DNA repair. Hence, defects in NE integrity and nuclear architecture cause drastic changes in cell homeosta… more
Amount: £1,084,517
The chemical biology and function of natural modified DNA bases in genomes
<p>I aim to elucidate the function of natural, chemically-modified DNA bases in the genomes of model organisms, using chemical&nbsp;biology and physical science approaches on genomic DNA. Modified bases are of fundamental importance to transcriptional programming and cell identity during and after development. The role of the cytosine derivative 5-formylcytosine and its influence on nucleosome fo… more
Amount: £2,198,391
A multi-disciplinary approach to understanding and improving hearing by cochlear implant users
<p>Cochlear implants (CIs) restore hearing by electrically stimulating the auditory nerve. This allows many CI users to understand speech well in quiet, but even the most successful have poor pitch perception and struggle in noisy situations. We believe there are two main reasons for these limitations.(i) Although it is possible to elicit different pitches by stimulating different electrodes, the… more
Amount: £1,727,476
Development of likelihood-based methods in structural biology
<p>I propose to build on our development of new likelihood-based methods for structural biology, transposing approaches that have had great impact in macromolecular crystallography to the new area of cryo-EM.&nbsp; 1) In crystallography we will enable the solution of difficult structures (poor data or poor starting models) that still evade current methods.&nbsp; New statistical innovations will a… more
Amount: £1,916,285
Molecular mechanisms of alternative splicing regulation
<p>Alternative pre-mRNA splicing (AS) is a widespread regulatory mechanism enabling individual genes to generate multiple protein isoforms. We have investigated the mechanisms controlling AS events that are regulated during the transition of smooth muscle cells (SMCs) between contractile and proliferative phenotypes. We have shown how the widely-expressed RNA binding proteins (RBPs) PTBP1 and MBN… more
Amount: £1,503,005
Fractionating the human frontoparietal cortex: combining meta-analytic and real-time optimization approaches
<p>Disruptions in the same set of frontal and parietal brain regions are seen across a striking range of psychiatric and neurological conditions. This network of regions has been referred to as <em>multiple-demand</em> (MD) system and can be divided into at least two closely coupled subnetworks. However, despite extensive research efforts, the specific functional mechanism each subnetwork support… more
Amount: £250,000