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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
Cellular Structural Biology
OXION - Membrane Transport in Health and Disease
Chromosome and Developmental Biology.
Genomic medicine and statistics
Defining host and viral factors that are associated with hepatitis B virus control and clearance in Caucasian and African adults.
HBV accounts for a significant global burden of liver disease. This project is founded on the urgent need to characterise T cell responses in order to enhance our understanding of differential outcomes of infection, and underpin future immunotherapeutic strategies. I will recruit a multi-centre cohort of adults with chronic hepatitis B infection (CHB) in Africa and the UK, to study factors associ… more
Spatio-temporally multiplexed 2-photon imaging determining neural coding principles of sensory perception.
How does the brain encode the contents of sensory perception and translate them into meaningful neuronal representations of our environment? Although we know approximately how sensory input is routed through different brain areas, each extracting distinct aspects of the percept, the neuronal language used to represent sensory experiences remains elusive. Our work aims is to unravel the coding str… more
Trade Liberalisation and Diet-Related Non-Communicable Diseases.
This research will empirically examine the effect of trade liberalisation on diet and alcohol-related non-communicable diseases (NCDs) with two key goals in mind. Firstly, this research aims to assess whether liberalisation increases or decreases unhealthy food and alcohol consumption via changing social environments. Elements of social environments known to affect food and alcohol consumption in… more
The Problem with Practicality: Rethinking the Function of Late-Medieval Medical Recipes 1400-1550.
I intend to examine late-medieval manuscripts containing English medical recipe collections, in order to establish a clearer and more nuanced understanding of their cultural functions. I aim to analyse the navigational aids, reader annotation and manuscript context of these collections, in order to complicate the current critical conception that they only or predominantly served practical functio… more
Membrane modulation in crucial virus-host interactions.
Viruses and their interactions with host cells provide attractive model systems for studying macromolecular interactions. The structural design of viruses provides a remarkable example of simplicity and functionality in biological systems. Viral particles and machineries work as highly effective molecular devices to mediate membrane traversal to transfer viral genomes and accessory proteins into … more
Calcium-sensing receptor (CaSR) - a G-protein coupled receptor (GPCR) - signalling pathways in health and disease.
The calcium-sensing receptor (CaSR), a G-protein-coupled receptor (GPCR) that is widely expressed, is critical for calcium homeostasis and also has non-calcitropic roles (e.g. development of neurons and lungs; cell fate; tumourigenesis; and gastro-entero-pancreatic physiology). We have shown that: mutations of the CaSR, the alpha-subunit of its associated G-protein (G-alpha-11), and the adaptor-p… more
The role of the nuclear exosome complex in RNA regulation.
Accurate regulation of RNA levels in eukaryotes is integral to many aspects of cellular metabolism including establishment of cell identity and survival. A conserved multisubunit exosome complex of 3'-5' exo- and endonucleases is absolutely essential for maintaining the proper levels of functional RNA and specific elimination of defective RNA in both nucleus and cytoplasm. However, the mechanisms… more
Time to Decide.
The objective of this proposal is to investigate the temporal dynamics of simple perceptual decisions in Drosophila, with a view toward uncovering general mechanisms of neural information processing at timescales from hundreds of milliseconds to several seconds. In his classical essay The Problem of Serial Order in Behavior, the psychologist Karl Lashley emphasized the ubiquity of brain processes… more
The evolutionary biology of antibiotic resistance.
Antibiotic resistance poses a growing threat to human health. Natural selection drives the spread and maintenance of antibiotic resistance, but most of our understanding of the evolution of resistance comes from simple in vitro experiments and animal models. My project will bridge the gap between clinical microbiology and evolutionary biology by elucidating the evolutionary processes that drive t… more
Harnessing Human Antibodies to Deliver Effective Immunoprophylaxis against Difficult Disease Targets.
Antibodies underpin effective vaccine-induced immunity, whilst monoclonal antibodies (mAbs) have come of age as effective biologicals. Nevertheless, effective antibody-mediated immunity can still fail to arise against numerous disease targets. This proposal seeks to understand the human antibody response against target antigens to enable the development of new vaccines or immunoprophylactic appro… more
First-in-human trial of an optimised lentiviral vector for cystic fibrosis gene therapy
Cystic Fibrosis (CF) is a genetic condition that shortens patients' lives, usually because of lung disease. A person with CF inherits two faulty copies of a gene called CFTR, one from each parent. Lacking normal CFTR, CF lungs become clogged with sticky mucus and cannot easily get rid of inhaled bacteria and viruses that damage the lungs. The annual cost of treating the 10,000 UK patients is ~£30… more
Invisible Crises, Neglected Histories: Malaria in Asia, c.1900-present.
In a landmark article in Nature (2005), a group of researchers including my collaborator Robert Snow argued that the incidence of severe malaria (caused by the P. falciparum parasite) outside of Africa and particularly in Asia had been massively under-estimated. There is also a dearth of information about the incidence and societal impact of the most common form of malaria in Asia (P. vivax), wh… more