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Implementation of ISARICC's 2018-2022 Strategic Plan
<p>Bridging funds for transition to ISARICC's 2018-2022 Strategic Plan</p>
Development of compounds that inhibit RAS-effector protein-protein interactions in cancer using a single antibody domain drug surrogate emulator approach
Prof Rabbitts and colleagues from the Weatherall Institute of Molecular Biology have been awarded Seeding Drug Discovery funding to develop small molecules specifically targeting the RAS-effector protein-protein interactions. The RAS family of oncogenes is among the most frequently mutated in human cancers. Using minimal antibody fragments, the group has characterized an anti-RAS VH segment whos… more
Public Engagement Provision.
Collaborative outreach programme with Mark Withers and the Orchestra of the Age of Enlightenment (OAE): This programme builds on a history of collaborations between Russell Foster and musician Mark Withers dating back to 1997 which includes a major education project, A Celebration of Life on Earth", with the OAE. We will start our work from scientific research into sleep, the eye and body clocks.… more
Public Engagement Provision
<table> <tbody> <tr> <td>Ageing societies and diseases of modern living require truly novel, efficacious and safe medicines. Increasing investment in R&D has not improved the efficiency of this endeavor. There is an urgent need for novel, validated drug targets. To facilitate this, the Wellcome Trust and other organisations have sponsored large-scale genome-… more
Open access award 2014/15.
The role of the innate immune system in repair and regeneration following myocardial infarction.
<table> <tbody> <tr> <td> <p>After myocardial infarction in the adult heart, a stereotyped innate immune response drives persistent inflammation, leading to impaired healing, scar formation, adverse remodelling and heart failure. In contrast, the murine neonatal heart heals by regeneration after injury, without scar or fibrosis. In both the adult and neonat… more
Using next generation chromatin conformation capture approaches to study the dynamics and
<p> </p> <p>Gene expression is controlled by complex networks of regulatory elements in the genome, involving promoters, enhancers, silencers and insulator elements. Chromatin conformation capture methods can be used to analyse these <em>cis</em>-acting networks by measuring the physical interactions between the regulatory elements involved. Recently, a high-throughput approach, Capture-C, h… more
Analysis of bacterial genetic variation through long and short read sequencing, using graphical
<p>This PhD focuses around the development of methods for representation and analysis of genomic variation using long and error-prone reads, such as those from Oxford Nanopore Technologies and Pacific Biosciences. There are two key goals. 1) Our group has recently developed a novel “FM-index-like” data structure that allows representation of a partial order alignment (related to a mul… more
Multisensory Convergence and Integration in Thalamic and Cortico-Thalamo-Cortical Circuitry
<p>The thalamus occupies a unique position. All sensory information, but olfaction, travels through the thalamus before reaching its cortical destination. Furthermore, it has been found to be mediating communication between several cortical areas. However, the functional anatomy and role of such cortico-thalamo-cortical circuits are poorly understood in sensory processing. The thalamus has also b… more
This is an application to fund a Community Engagement and Ethics Coordinator in the Thailand Major Overseas Programme for two years.
The Thailand Overseas Programme has more than three decades of experience in conducting clinical trials in resourced limited settings in Asia and Africa. Increasingly we recognise that engaging with the communities we work in is essential to the success of these trials, regardless of geography and discipline. Equally important, is identifying and addressing ethical issues related to medical resea… more
Tracing early mammalian lineage decisions by single cell genomics.
Lewis Wolpert famously called gastrulation the most important time in your life. During this fascinating process, a pluripotent stem cell population in the early embryo gives rise to the three germ layers from which all organ systems develop. Cell signalling and transcriptional networks are known to regulate aspects of gastrulation, but the precise mechanisms have not been investigated at the sin… more
Characterising control of mycobacterial growth in patients with TB disease and M. tuberculosis infection.
TB can be viewed as a continuous spectrum extending from sterilising immunity, quiescent M. tuberculosis (M.tb) infection, and active disease. Identifying phenotypic subgroups within this spectrum is challenging and the tools we use are currently imperfect. An understanding of protective immunity against TB disease is lacking, as are predictors of risk of disease progression, biomarkers of respon… more
Effect of beta2-adrenergic receptor agonists on the acetylcholine receptor clustering pathway in congenital myasthenic syndromes.
Congenital myasthenia contains a group of inherited disorders affecting neuromuscular transmission. The host laboratory has previously shown that beta2-adrenergic agonists, such as salbutamol, are particularly beneficial in a subgroup of patients with congenital myasthenia, typically involving DOK7 mutations. DOK7 is a member of the acetylcholine receptor (AChR) clustering pathway, a pathway cruc… more
Role of interleukin 33 in intestinal homeostasis
<table> <tbody> <tr> <td>This research project will focus on the identification of the role of interleukin 33 (IL-33) in intestinal homeostasis. IL-33 belongs to the IL-1 family and has been shown to mediate both pro-inflammatory and anti-inflammatory processes depending on the disease context. Although IL-33 is produced in high amounts in the intestine little is known about its rol… more
Developing a novel single dose prime-boost vaccine against malaria
<table> <tbody> <tr> <td>The main goal of this project is to develop a new vaccine delivery platform for a single dose prime-boost immunisation regime that would be applicable to current and future vaccines requiring a prime-boost approach. This novel platform is based on the technological advance of the production ofmicrocapsules from biodegradable polymers, which can… more
Childhood pneumococcal pneumonia in Nepal: novel immunodiagnostic methods and transcriptomic investigation of pathophysiology
<Synopsis>1.3 million children <5 years of age die from pneumonia annually worldwide, with Streptococcus pneumoniae (pneumococcus) responsible for 740 000 of these deaths, despite increasing uptake of pneumococcal conjugate vaccines (PCV). However, accurate diagnostics for pneumococcal pneumonia, and a clear characterisation of the pathway from healthy nasopharyngeal carriage to disease, are l… more
Understanding the role of the RNA-binding protein Mmi1 in coupling transcription and RNA processing by the exosome complex.
Regulation of gene expression in eukaryotes is integral to establishment of the cell identity and survival. Synthesis of pre-mRNA in eukaryotes is catalyzed by RNA polymerase II (Pol II). The level and quality of RNA is controlled by the RNA gsurveillance h machinery represented by the highly conserved exosome complex of 3'-5' exonucleases, which is therefore responsible for establishing the bala… more
Genetic dissections of hippocampal function.
The aim is to provide a unifying account of the hippocampus, using the latest molecular biological techniques, along with a novel in vivo voltammetric approach for recording tissue oxygen concentrations. I will investigate the role of synaptic plasticity in two, distinct forms of hippocampus-dependent spatial memory, and test the novel hypothesis that SRM and SWM reflect associative and non-assoc… more
The impact of vaccine platform on the cellular drivers of humoral immunity
<p>The focus of this Fellowship proposal is on how vaccine platform affects the cellular drivers of humoral immunity, specifically memory B cells (mBCs) and T follicular helper (Tfh) cells. I will compare the leading <em>Plasmodium falciparum</em> blood-stage malaria candidate – RH5 – in two vaccine platforms: heterologous viral vectors (chimp adenovirus 63 prime, Modified Vaccinia An… more