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Results

The Total Archive: Dreams of Universal Knowledge from the Encyclopaedia to Big Data. 30 Jan 2015

The conference 'The Total Archive' and associated special issue of the journal LIMN deals with schemes for universal knowledge, from mass bio-sample collection and global demography to representations of totalities in film, fiction and visual art. The conference seeks to interrogate the practices of Big Data and the identity politics of sciences with grand explanatory claims, for example modern genomics. The conference takes place on March 19/20, 2015, at the Centre for Research in the Arts, Hum anities and Social Sciences (CRASSH), University of Cambridge. In addition to the urgent need to contextualise Big Data (see: http://www.mpiwg-berlin.mpg.de/en/research/projects/DeptII_Aronova_Oertzen_Sepkoski_Historicizing), the conference is timely because of the increasing use of large data-sets and aspirations to totality in the humanities themselves. For example CRASSH's own 'Visual Representations of the Third Plague Pandemic' is one such project represented at the conference. Theme s of mass data collection are also important outside the academy, and so the conference will feature a public lecture (by the literary theorist Katherine Hayles), and essays will be published in the popular open access journal LIMN (www.limn.it), which has agreed in principle to run a special issue on the topic.

Amount: £2,800
Funder: The Wellcome Trust
Recipient: University of Cambridge

A Two-day Conference on the Human Right to Health, Universal Health Coverage and Priority Setting. 27 Oct 2014

This grant would be used to fund a two-day conference exploring the various tensions between what the UN refers to as the progressive realisation of the human right to health, the international effort to secure universal health coverage and the inevitable need to set priorities between different treatments and services. The conference would bring together three research centres within UCL (the Institute of Global Health, the Institute of Global Governance and the Centre for Philosophy, Justi ce and Health) to hear new evidence from researchers, policy-makers and practitioners from both the UK and abroad. The conference would: i) explore existing policy drives towards HRH, universal health coverage and priority setting activities; ii) reflect upon conceptual and ethical tensions between such policies; and iii) assess the feasibility of solutions aimed at resolving this tension. The conference's main output would be a consensus statement, drawn up by Benedict Rumbold and circula ted to delegates before the meeting and discussed by attendees on Day Two of the conference itself, setting out the delegates thoughts on the next steps towards remedying the current conflict between HRH, the drive towards Universal Coverage and priority setting.

Amount: £4,760
Funder: The Wellcome Trust
Recipient: University College London

Functional neuromics of the cerebral cortex. 21 Jul 2015

Cortical circuits comprise multiple classes of neurons and glia, whose interactions govern perception, behaviour, and thought. We propose to combine several new techniques to probe this circuitry with unprecedented precision by identifying, monitoring, and controlling the participating cells. We will: 1. Provide a definitive taxonomy of cortical cell classes. By applying single-cell RNA sequencing to tens of thousands of neocortical and hippocampal cells, we will identify cell classes and su bclasses, together with marker genes that in combination identify them. 2. Understand the anatomical organization of these classes. By applying in situ transcriptomics to cortical tissue, we will understand the position of each class in the circuit, and determine the molecular identity of selected projection classes. 3. Understand how these classes participate in sensory processing and behaviour. We will record the activity of neurons and glia in the neocortex and hippocampus of behaving mice, then classify the recorded cells by retrospective in situ transcriptomics. 4. Identify causal interactions among cell classes in vivo. We will reveal the causal influence of molecularly identified cells on the network by stimulating them using 2-photon optogenetics, while recording population activity. These data will constrain mechanistic models of the underlying circuit.

Amount: £4,189,482
Funder: The Wellcome Trust
Recipient: University College London

Diabetes and Inflammation Laboratory. 21 Apr 2015

Our goal is to identify clinical interventions in patients recently diagnosed with, or children at high risk of developing, type 1 diabetes (T1D), thereby maximising the health benefits of genetics and genomics in this common immune disorder. Our studies in T1D serve as a model for the investigation of other diseases and their treatment. We will take specific steps towards achieving this goal during the next five year programme: (1) Genetics. Define the genetic basis of T1D by fine-mapping di sease-associated causal variants and haplotypes, identify their target genes, and investigate the regulation of these genes before and after cell activation/differentiation. (2) Phenotypes and mechanisms. Identify aberrant cellular interactions and pathways caused by susceptibility genes that mediate a loss of immune tolerance to insulin-producing beta cells culminating in their destruction. These will provide potential targets for therapeutic intervention, as demonstrated by our work in the I L-2 pathway. (3) Experimental medicine. Complete our mechanistic investigations of the effects of IL-2 administration in patients, as a prelude to testing the efficacy of ultra-low dose IL-2 in the preservation of C-peptide and beta-cell function. Investigate, using the same mechanistic approach and depending on our emerging knowledge, another potential therapeutic.

Amount: £8,289,795
Funder: The Wellcome Trust
Recipient: University of Cambridge

A high resolution platform to capture the dynamic spatial proteome. 11 Jun 2015

This proposal aims to create a platform for mapping the subcellular location of a substantial proportion of the proteome in a single experiment with high resolution. It is based on preliminary work carried out by the Lilley group in collaboration with Thermo, giving tantalising insight into what this technology could deliver if developed further into a fit-for-purpose spatial proteomics platform. The key objectives are: 1. Expand the sampling of subcellular proteome to locate proteins to multi ple compartments. 2. Capture information of the effect of post-transcriptional and post-translational modification on spatial location. 3. Develop approaches to enable the mapping of the dynamic subcellular redistribution of proteins upon biological perturbation. 4. Incorporate work-flows that will deliver spatial information about targeted sub-sets of proteins and integration with whole cell maps. 5. Develop cross-linking strategies to preserve interactions of peripheral membrane proteins and between components of multi-protein complexes. 6. Develop a set of bespoke informatics tools facilitating the application of pattern recognition for robust analysis. 7. Create a GUI to facilitate community-wide interrogation of cellular maps. 8. Develop on-line protocols. 9. Apply the technology to the co-applicants and collaborators research, adding value to projects already funded by the Wellcome Trust.

Amount: £200,788
Funder: The Wellcome Trust
Recipient: University of Cambridge

New genetic, imaging and microfluidics technologies for single cell genomics 11 Jun 2015

Two major limitations of single cell genomics is (i) the loss of information about the original location within the sample of the sequenced cell and (ii) low throughput at high cost with only hundreds of cells analysed per day. Miniaturising single cell analysis to pico-litre volumes will critically facilitate higher throughput (10^4 - 10^6cells) at lower costs and sidesteps restrictions in handling. Combined with genetic technologies to record lineage history and spatially localise cells this w ill allow questions to be address at single cell resolution that are essential to understand cell diversification following tissue-contextual interactions and the impact it has on gene transcription. 1) We will develop microfluidics based devices to increase sequencing throughput by increasing the number of cells processed at a low cost, and at the same time enabling the complex handling and manipulation of small cell numbers with minimal loss. 2) We will develop genetic technology to: i) record within the genome the lineage history of each cell, for readout at any stage of interest and ii) to provide a unique fluorescent signature to cells to enable us to provide spatial and temporal context to their transcriptional profiles.

Amount: £410,687
Funder: The Wellcome Trust
Recipient: University of Cambridge

Construction and testing of a whole-cell arsenic biosensor with a simple visual readout for field use 29 May 2015

Arsenicosis from chronic consumption of contaminated ground water affects virtually all organs and tissues where skin lesions, bronchitis, gastroenteritis and ultimately a range of cancers are typical pathologies. Although arsenic contamination of drinking water is a global problem, it most seriously affects on the order of 100 million people in some of the poorest regions on earth including India/West Bengal, Bangladesh and Nepal. Prof James Ajioka's team at Cambridge University and Prof French at Edinburgh University are aiming to construct an inexpensive and reliable kit to assess arsenic contamination in drinking water in rural villages. Based on the observation that some bacteria detect arsenic, they will engineer an arsenic sensing device based on the Bacillus subtilis arsenic operon. This biosensor will be combined with a reporter system based on the violacein operon, resulting in bacteria that would turn green when it detects very low, safe levels of arsenic in the drinking water, but if the arsenic contamination is at a dangerous level, it will turn violet. The transcriptional signal to drive the pigment device in the bacteria can be tuned to respond to arsenic levels within definition of WHO safe or dangerous levels. The kit will be based on a weakened strain of the harmless soil dwelling bacteria, B. subtilis, housed in a robust plastic container to further reduce any risk and for easy, environmentally friendly deactivation/disposal.

Amount: £33,171
Funder: The Wellcome Trust
Recipient: University of Cambridge

Development of TIPS microspheres for the treatment of fistulas 15 Dec 2014

Perianal fistulas are abnormal channels formed between the anal canal and the skin surface. Existing treatments to close these channels typically involve medical and surgical approaches, however both have limitations. Medical agents are usually delivered systematically, but this may predispose the patient to severe infection and autoimmune reactions. Surgery using existing anal fistula plugs is successful in the treatment of simple fistulas but is associated with a high failure rate in more complex fistulas and in patients with Crohn’s disease. Dr Richard Day from University College London has received a Translation Award to develop a potential solution to this problem. He and his team have developed microspheres that, when packed into a fistula, provide a ’scaffold’ that cells can grow between and into. As the microspheres dissolve, they are replaced by new tissue to heal the fistula. With this award, Dr Day and his team aim to demonstrate that the microspheres are safe when implanted into perianal fistulas in humans.

Amount: £91,754
Funder: The Wellcome Trust
Recipient: University College London

Soft Robotic Total Larynx Replacement 27 Jan 2015

The technology to be developed combines novel soft robotics with proven biocompatible materials and electromyography to produce a synthetic total larynx replacement. T radWonal robotic approaches that utilise rigid material are not sufted for long term integration in the larynx due to insufficient replication of the natural musculature and physiology and the requirement for multi-component designs that increase infection risks. By exploiting advances in soft robotics, which utilises flexible and elastic intelligent materials to morph compliant structures into complex shapes, we bypass the difficultiesencountered with traditional, hard, robotics. This enables the manufacture of a monolithic synthetic larynx, made biocompatible through combination with a clinically proven airway implantable synthetic polymer. The device is controlled by electromyography of the strap muscles and muscles of the floor of the mouth, which can be preserved in laryngectomy, to infer when the patient is speaking or swallowing. The implanted device will robustly replicate the core functionality of the larynx (aspiration prevention, respiration and phonation) with a failsafe modality.

Amount: £1,395,353
Funder: The Wellcome Trust
Recipient: University College London

Interdisciplinary Training Programme for Clinicians in Translational Medicine and Therapeutics at the University of Cambridge: Support for the 2014 MPhil Appointments. 15 Dec 2014

We propose an innovative training scheme for Translational Medicine and Therapeutics (TMAT) which builds on the exceptional conjunction on the Cambridge campus of leading scientists and clinical specialists, with an industrial research environment embraced both by international pharmaceutical and local biotech companies. Much of this is found under the same roof, the Addenbrookes Centre for Clinical Investigation (ACCI), with a track record of integrated training: academic with industrial, clinical with scientific, pharmacology & therapeutics with patient-based specialties. The novel TMAT programme will attract the brightest candidates at several levels of seniority, ranging from MB PhD students to clinical lecturers, some wishing translational skills in their chosen specialty, others not yet differentiated who may become future leaders and teachers of TMAT. Each trainee will have a customised programme. Part of this will be a bespoke, modular MSc modelled on the well-known small-group lectures and supervisions of the Cambridge final year undergraduate courses. However the centrepiece for most candidates will be a PhD including formal teaching in a wide range of translational and pharmacological skills, and a project which takes proof-of-concept studies in cell or animal systems forward to proof-of-concept studies in humans. We have assembled an outstanding faculty of PhD supervisors spanning a wide choice of skills and experience in basic and clinical science. All trainees will have the opportunity for hands-on exposure to the design and conduct of experimental medicine studies investigating the therapeutic potential of new drugs, in collaboration with our industrial partner, GlaxoSmithKline (GSK). Our product will be a new generation of clinician scientists with 360-degree vision of the complex landscape of modern therapeutic medicine, who can rise to the challenges and opportunities of 21st century drug development.

Amount: £28,140
Funder: The Wellcome Trust
Recipient: University of Cambridge

Biomedical Vacation Scholarship 22 Jun 2015

Not available

Amount: £19,750
Funder: The Wellcome Trust
Recipient: University College London

Biomedical Vacation Scholarship 22 Jun 2015

Not available

Amount: £7,750
Funder: The Wellcome Trust
Recipient: University of Cambridge

Cambridge Stem Cell Institute Four year PhD studentships - Stem Cell Biology - Sarah Foerster 30 Jan 2015

This proposal is to facilitate creation of a world-leading centre for fundamental and translational stem cell research. The Cambridge Stem Cell Institute (SCI) will build upon previous Wellcome Trust and Medical Research Council funding by drawing together 30 research teams into a cohesive centre. These groups will ultimately be co-located in a purpose-designed 8000m2 facility to be constructed on the Cambridge Biomedical Research Campus. Platform technologies supported by a Centre grant will en able SCI to recruit and retain the most talented investigators and empower them to make ground-breaking advances in understanding stem cells and their medical applications. Fundamental research will focus at the molecular level on mechanisms of self-renewal, commitment, differentiation and reprogramming. Functional studies will address the role of stem cells in development, repair, ageing, physiology and pathologies including cancer. Disease-specific induced pluripotent stem cells will be exploi ted to unravel mechanisms of cellular pathogenesis and define drug targets. Strategies to mobilise endogenous stem

Amount: £64,535
Funder: The Wellcome Trust
Recipient: University of Cambridge

Cambridge Stem Cell Institute Four year PhD studentships - Stem Cell Biology- Samuel Myers 30 Jan 2015

This proposal is to facilitate creation of a world-leading centre for fundamental and translational stem cell research. The Cambridge Stem Cell Institute (SCI) will build upon previous Wellcome Trust and Medical Research Council funding by drawing together 30 research teams into a cohesive centre. These groups will ultimately be co-located in a purpose-designed 8000m2 facility to be constructed on the Cambridge Biomedical Research Campus. Platform technologies supported by a Centre grant will en able SCI to recruit and retain the most talented investigators and empower them to make ground-breaking advances in understanding stem cells and their medical applications. Fundamental research will focus at the molecular level on mechanisms of self-renewal, commitment, differentiation and reprogramming. Functional studies will address the role of stem cells in development, repair, ageing, physiology and pathologies including cancer. Disease-specific induced pluripotent stem cells will be exploi ted to unravel mechanisms of cellular pathogenesis and define drug targets. Strategies to mobilise endogenous stem

Amount: £11,112
Funder: The Wellcome Trust
Recipient: University of Cambridge

Cambridge Stem Cell Institute Four year PhD studentships - Stem Cell Biology - Loukia Yiangou 30 Jan 2015

This proposal is to facilitate creation of a world-leading centre for fundamental and translational stem cell research. The Cambridge Stem Cell Institute (SCI) will build upon previous Wellcome Trust and Medical Research Council funding by drawing together 30 research teams into a cohesive centre. These groups will ultimately be co-located in a purpose-designed 8000m2 facility to be constructed on the Cambridge Biomedical Research Campus. Platform technologies supported by a Centre grant will en able SCI to recruit and retain the most talented investigators and empower them to make ground-breaking advances in understanding stem cells and their medical applications. Fundamental research will focus at the molecular level on mechanisms of self-renewal, commitment, differentiation and reprogramming. Functional studies will address the role of stem cells in development, repair, ageing, physiology and pathologies including cancer. Disease-specific induced pluripotent stem cells will be exploi ted to unravel mechanisms of cellular pathogenesis and define drug targets. Strategies to mobilise endogenous stem

Amount: £29,998
Funder: The Wellcome Trust
Recipient: University of Cambridge

2 month costed extension 20 Jul 2015

This application requests the continuation of core support to the Wellcome Trust/Cancer Research UK Gurdon Institute, which is an integral part of the University of Cambridge. The aim of the Institute is to contribute to an understanding of normal animal development, including the processes of cell differentiation, proliferation and morphogenesis, and to explain how cancers arise when these processes go wrong. The Institute sets out to achieve these objectives by recruiting excellent scientists and providing them with the best possible environment and facilities for their work. This is made possible by our core funding, which provides technical, administrative and secretarial support to our research groups, as well as expert assistance in bioinformatics, imaging and computing. Core support also ensures that our researchers have access to state of the art facilities, and we are requesting funding for advanced microscopy and high throughput sequencing equipment, and continuing support fo r our mouse facility. Our major goal for the next quinquennium is to produce world class research at the interface between developmental biology and cancer. To achieve this, we will increasingly use genome-wide approaches and quantitative proteomics, and we therefore plan to establish facilities for high throughput sequencing, high content screening, and mass spectroscopy

Amount: £339,619
Funder: The Wellcome Trust
Recipient: University of Cambridge

2 month costed extension 20 Jul 2015

Not available

Amount: £252,519
Funder: The Wellcome Trust
Recipient: University College London

Exploring the neurocomputational mechanisms of adaptive and pathological anxiety. 12 Jan 2015

At present the majority of people with anxiety fail to respond to their first treatment. Refining our understanding of the mechanisms underpinning anxiety, as well as the process by which adaptive anxiety becomes maladaptive is critical in order to improve diagnosis and treatment outcomes. To this end, the objective for this collaborative doctoral research project between UCL and the NIMH is to investigate the neurocomputational basis of adaptive and pathological anxiety. Specifically, what are the decision-making variables involved in adaptive and pathological anxiety and what are the underlying computations in the neural level?

Amount: £80,000
Funder: The Wellcome Trust
Recipient: University College London

Investigating the role of TL1A-DR3 in immune complex-mediated autoimmune disease. 12 Jan 2015

In this project we propose to focus on the role of the DR3-TL1A axis in autoimmune disease and more specifically on its involvement in lupus nephritis. We will determine which subset of kidney-resident mononuclear phagocytes express TL1A following immune complex-dependent FcgammaR-cross-linking. We will also investigate the relative importance of DR3 expression on myeloid cells versus lymphocytes in disease pathogenesis. Finally we will address how the myeloid cells and lymphocytes interact in the kidney in vivo and determine the role of the DR3-TL1A axis in these interactions

Amount: £80,000
Funder: The Wellcome Trust
Recipient: University of Cambridge