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Paul Hamlyn Foundation
The Wellcome Trust
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University College London
University of East Anglia
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£1,000 - £5,000

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Results

Mechanisms and plasticity of dendritic temporal sequence processing. 13 Feb 2012

The mechanism by which neurons detect, organize and process numerous chemical and electrical signals is a fundamental problem in modern neuroscience. For example, the ability to discriminate spatiotemporal sequences of synaptic input has been suggested to be important for generating efficient coding schemes, and input sequence detection in general is a computation essential for animal behaviour. Previous work showed that dendrites could be responsive to the "direction" of temporally spaced inputs due to their cable filtering properties, suggesting that single neurons could act as basic sequence detectors. This "passive" direction selectivity was confirmed experimentally by Branco and colleagues, who also discovered that "active" NMDA receptor conductance recruitment dramatically enhances the direction sensitivity of somatic responses. In addition, Branco et al. 3 found that dendrites could discriminate not only directional sequences, bu1 also a wide range of spatiotemporal patterns. However, the role and impact of dendritic sequence processing is unknown for computation in different cortical areas and under different conditions. I plan to concentrate on two broad questions addressing how dendritic mechanisms can optimally discriminate sequences and potentially store selected input patterns. First, I will concentrate on the types of spatiotemporal patterns that can be distinguished from each other. Second, I will investigate whether specific input sequences can be stored, by probing plasticity processes triggered by different input patterns. Optimal conditions for dendritic pattern recognition. What is the optimal spatial distribution of inputs? What is the "optimal dendrite"? Interaction of patterns on the dendrite. The interaction of backpropagating action potential and patterned inputs. Influence of background noise. Sources of calcium ? pharmacology. Tthe effects of neuromodulation. Plasticity triggered.by patterned input. Plasticity induction readouts. Plasticity induction protocols - repetition of the same input pattern and pattern and action-potential combination Effect of neuromodulation in regulating of pattern-induced plasticity.

Amount: £14,356
Funder: The Wellcome Trust
Recipient: University College London

Olig2 and the regulation of neural stem cell fate. 27 Jan 2012

During development of the central nervous system (CNS), neuroepithelial stem cells (NSCs), residing in the ventricular zones (VZ) of the embryonic brain and spinal cord, divide and differentiate to generate all the neurons and glial cells (astrocytes and oligodendrocytes) of the mature CNS. Typically, neurons form before glia. In the ventral spinal cord, for example, embryonic NSCs of the pMN progenitor domain generate several subtypes of motor neurons (MNs) before switching abruptly (at E12.5 in mouse) to production of oligodendrocyte precursors (OLPs). The OLPs then migrate away from the VZ into all parts of the spinal cord before associating with axons, differentiating into post-mitotic oligodendrocytes (OLs) and synthesizing myelin. We aim to address how NSCs switch at a predetermined time from neuron to glial production ? specifically, the mechanism of the MN-OLP fate switch in the ventral spinal cord. Broadly, the proposed project aims to characterize the role and regulation of the basic helix-loophelix transcription factor Olig2 in the MN-OLP fate-switch. Recent work from the Richardson lab showed that a specific serine residue (S147) in Olig2 is phosphorylated during MN specification and de-phosphorylated at the switch to OLP production. What triggers de-phosphorylation of Olig2 at the time of the MN-OLP switch? The sequence surrounding S147 conforms to a protein kinase-A target site, but the identity of the putative phosphatase responsible for dephosphorylation has not been established. What are the targets and co-factors of Olig2 in its different phosphorylated states that coordinate the temporally-defined switch in NSC fate? And what are the functions of the other predicted Olig2 phosphorylation states? This project will involve three distinct lines of investigation. 1: Characterizing the expression of candidate phosphatases/phosphatase inhibitors in the ventral spinal cord at the time of the MNOLP fate-switch. 2: Identifying target genes of Olig2 in its phosphorylated and de-phosphorylated states. 3: Characterizing the developmental function of another Olig2 phosphorylation site, S263, a potential target of p38 mitogen-activated protein kinase (MAPK).

Amount: £31,882
Funder: The Wellcome Trust
Recipient: University College London

Identifying mechanisms of mechanosensation in the Drosophila notum that contribute to the control of epithelial junction remodelling. 27 Jan 2012

When two epithelial cells make contact they form a stable cell adhesion complex that finally results in the formation of an epithelium. However when two mesenchymal cells make contact the outcome is completely different: they do not form a permanent adhesion complex and very frequently they move away from each other in a behavior called contact inhibition of locomotion [1]. Intriguingly, cell adhesion molecules such as cadherins are known to be involved in both kinds of cell interaction. The formation and dynamics of the adhesion complex in epithelial cells has been extensively studied [2], but the study of cell-cell interactions and cell adhesion in mesenchymal cells has been rather neglected. The aim of this project is to compare cell adhesion complex formation between epithelial cells and between mesenchymal cells, in order to understand the different outcomes of these two cell interactions. This knowledge would help us to better understand important processes such as epithelial-to-mesenchymal transition and contact inhibition of locomotion; two cell behaviors that are central to both cancer metastasis and cell migration during embryo development. We will use two embryonic cell populations whose behavior has been very well characterized in our lab: neural crest (as a mesenchymal cell type) and placode cells (as an epithelial cell type). Most of the experiments will be performed using Xenopus cells cultured in vitro, but we will also analyze cell behavior in vivo, using zebrafish and Xenopus embryos. The cell adhesion complex has been well characterized in epithelial cells, and several key molecules have been described, such as cadherins, catenins, and elements of the cytoskeleton like actin and myosin. In addition, the regulation of small GTPases, such as RhoA and Rac, has been shown to be essential for the formation and maintenance of epithelial junctions. In this project, we will study in placode (epithelial) and neural crest (mesenchymal) cells: i) the dynamic localization of molecules of the cell adhesion complex during cell contact ii) the dynamics of small GTPases during cell contact and their regulation by elements of the adhesion complex. iii) From the above experiments we expect to find the key elements that regulate the different outcome of epithelial and mesenchymal cell-cell contacts. Based on these results, we will perform functional studies with these molecules in order to change a mesenchymal cell-cell contact into an epithelial interaction and vice versa.

Amount: £3,500
Funder: The Wellcome Trust
Recipient: University College London

VEGF signalling in the nervous system. 27 Jan 2012

This project aims to examine if VEGF-C patterns the nervous system during axon guidance or synapse formation, and to define the molecular pathway by which VEGF-A signals in neurons independently of its role in blood vessels. Define the role of VEGF-C and its receptor VEGFR3 in axon pathfinding Determine if VEGF-A and VEGF-C function co-operatively to control axon pathfinding Identify NRP1 co-receptor(s) essential for VEGF-A signalling in neurons Examine if VEGF-A and/or VEGF-C control synapse development and function

Amount: £29,300
Funder: The Wellcome Trust
Recipient: University College London

What is the difference between epithelial and mesenchymal cell junctions: understanding the molecular basis of contact inhibition of locomotion and epithelial-mesenchymal transition. 27 Jan 2012

When two epithelial cells make contact they form a stable cell adhesion complex that finally results in the formation of an epithelium. However when two mesenchymal cells make contact the outcome is completely different: they do not form a permanent adhesion complex and very frequently they move away from each other in a behavior called contact inhibition of locomotion [1]. Intriguingly, cell adhesion molecules such as cadherins are known to be involved in both kinds of cell interaction. The formation and dynamics of the adhesion complex in epithelial cells has been extensively studied [2], but the study of cell-cell interactions and cell adhesion in mesenchymal cells has been rather neglected. The aim of this project is to compare cell adhesion complex formation between epithelial cells and between mesenchymal cells, in order to understand the different outcomes of these two cell interactions. This knowledge would help us to better understand important processes such as epithelial-to-mesenchymal transition and contact inhibition of locomotion; two cell behaviors that are central to both cancer metastasis and cell migration during embryo development. We will use two embryonic cell populations whose behavior has been very well characterized in our lab: neural crest (as a mesenchymal cell type) and placode cells (as an epithelial cell type). Most of the experiments will be performed using Xenopus cells cultured in vitro, but we will also analyze cell behavior in vivo, using zebrafish and Xenopus embryos. The cell adhesion complex has been well characterized in epithelial cells, and several key molecules have been described, such as cadherins, catenins, and elements of the cytoskeleton like actin and myosin. In addition, the regulation of small GTPases, such as RhoA and Rac, has been shown to be essential for the formation and maintenance of epithelial junctions. In this project, we will study in placode (epithelial) and neural crest (mesenchymal) cells: i) the dynamic localization of molecules of the cell adhesion complex during cell contact ii) the dynamics of small GTPases during cell contact and their regulation by elements of the adhesion complex. iii) From the above experiments we expect to find the key elements that regulate the different outcome of epithelial and mesenchymal cell-cell contacts. Based on these results, we will perform functional studies with these molecules in order to change a mesenchymal cell-cell contact into an epithelial interaction and vice versa.

Amount: £40,170
Funder: The Wellcome Trust
Recipient: University College London

Prenatal stem cell gene therapy for Wilson's Disease using amniotic fluid stem cells. 31 May 2012

Advances in prenatal diagnosis have led to the development of fetal therapies for inherited disorders. Stem cell and gene transfer techniques have shown thegreatest potential for use in the fetus, but their clinical utility has been limited by poor efficacy and concerns about safety. A novel approach that may address these limitations is stem cell-gene therapy with autologous amniotic fluid stem cells (AFS). These cells could undergo genetic modification in vitro and subsequently injected to the same fetus without the risk of an immune reaction/rejection. The proposed programme of work will investigate thetherapeutic potential of stem cell-gene transfer with AFS in Wilson's disease.This is an autosomal recessive disorder of copper metabolism that can be diagnosed in utero, and is caused by a mutation in the gene coding for the copper transport protein ATP7B. A model of Wilson's disease in ATP7B gene "knockout" mice will be used to test the hypothesis that correction of the genetic defect in autologous AFS, followed by in prenatal administration has long-term salutary effects effect in this setting. Key goals of the fellowshipare to maximise transduction of isolated AFS with functional ATP7B gene, optimise in utero transplantation of transduced AFS, and compare the therapeutic efficacy of AFS cell-gene transfer with other modes of fetal intervention for Wilson's disease.

Amount: £318,402
Funder: The Wellcome Trust
Recipient: University College London

Predicting language outcome and recovery after stroke. 07 Dec 2011

The main goal is to provide proof of principle for a clinically useful tool that will predict recovery of language abilities after stroke. There are three separate but interacting lines of research, to be conducted in parallel: (A) Using structural neuroimaging and behavioural assessments, we will identify lesion and non-lesion factors that are most likely, and least likely, to cause long term communication difficulties. The influence of the identified factors will be tracked over months and years following the stroke to understand how recovery unfolds over time. (B) Using functional neuroimaging and dynamic causal modelling, we will map the brain areas that are activated when the patient is speaking or comprehending speech. This will provide a mechanistic understanding of the language pathways that are able to support recovery after damage to the normal system. (C) We will develop an easy-to-use web-based system that will provide patients, their carers and clinicians with t he likely time course of recovery on the basis of probabilistic summaries of other patients in our database who have corresponding brain damage according to the carefully constrained criteria developed in (A).

Amount: £1,742,648
Funder: The Wellcome Trust
Recipient: University College London

Ion channels related to neutrophil NADPH oxidase. 17 Sep 2012

The neutrophil leukocyte is the primary cell involved in the killing and digestion of bacteria and fungi. The NADPH oxidase is an electron transport chain in the wall of the phagocytic vacuole which is essential for the killingof the contained microbe, and when defective, causes severe immunodeficiency.The oxidase passes electrons onto O2 to produce reactive oxygen species (ROS) and these ROS were thought to be responsible for microbial killing. We have shown that this is not the case and tha t the microbes are killed by granule enzymes released into the vacuole from cytoplasmic granules, and that the oxidase activates these enzymes by altering the pH and ionic composition in the vacuole. The ion fluxes are driven by the requirement to compensate the charge generated across the phagosomal membrane by electron transport which was thought to be accomplished by H+ flux through proton channels. K+ flux through BKCa-like channels is essential for oxidase activity, and consequently, microb ial killing and Cl- fluxes compensate most of the charge.In addition Na+/H+ exchange is important for the regulation of pH. We propose to characterise these ion channels, and to elucidate the mechanisms underlyingthe coupling of these processes to the oxidase.

Amount: £74,000
Funder: The Wellcome Trust
Recipient: University College London

Reducing sedentary behaviour in older adults: Development of a brief habit-based intervention. 07 Nov 2011

Physical activity in later life can improve health and quality of life, yet around 30% of adults aged 65-74 in England do less than 10 consecutive minutes of leisure-time activity a month. Previous activity promotion initiatives for older adults have failed to have real-world impact, perhaps because targets (e.g. 150 minutes of activity per week) have been unrealistic, or because observed changes in activity have been dependent on external support, so that when the intervention period ends so too does engagement in activity. We will design and assess the feasibility of a novel intervention to promote activity among sedentary older adults. The work is novel in two aspects: first, we focus on promoting activity by recommending small and easily-adopted changes to existing routines, and second, we aim to create 'activity habits' which will persist after the intervention has ended. Our intervention is based on recent advances in psychological theory which show that, if an activity is performed repeatedly in the same situation, it becomes a relatively effortless and automatic response to that situation (i.e. a 'habit'). Our work follows a recent weight-loss intervention in which simple written advice on how to form eating and activity 'habits' was provided, and which led users to form 'habits' and lose more weight than a control group. We propose three studies. In Study 1, a panel of 20 sedentary older adults, recruited via Age UK, will brainstorm ideas for activities that they could feasibly and consistently undertake (e.g. climbing stairs, walking, stretching and balancing exercises). A group of experts will then draft a series of recommended activities that could feasibly become 'habitual'. When both the older adult panel and the experts agree on the feasibility of the recommendations, a second panel of older adults will rate the recommendations for ease of understanding, whether they are motivated or likely to perform them, and how difficult they would be to perform. In Study 2, 30 sedentary older adults with no disabling physical impairments will be recruited via Age UK and given the recommendations, together with a tick-sheet to monitor adherence. They will be asked to return at four and eight weeks later for assessment of 'habit' formation, activity and health. We will assess rates of adherence and attrition, changes in 'habit' and activity, and whether intervention users felt that additional support (e.g. telephone counselling, community support) would assist them in adhering to the recommendations. In Study 3, a small-scale controlled trial will be undertaken to evaluate the intervention in a primary care setting. 120 sedentary older adults with no disabling physical impairments will be allocated to receive either the 'activity habit' recommendations (supplemented with any necessary additional support identified via Study 2), or a control treatment which promotes activity in older adulthood but not 'habit' formation. We will assess rates of recruitment, adherence and attrition, and changes in 'habit', activity, health and wellbeing. This study would generate an estimate of effect size for a subsequent full randomised controlled trial.

Amount: £54,590
Funder: The Wellcome Trust
Recipient: University College London

A statistical approach to the understanding of mutational processes in the human genome and their impact on evolution, health and disease. 12 Dec 2011

Germline genomic instability is the hypothesis that the architecture of the genome can increase the local mutation rate mostly through homologous regions promoting structural variation (SV) through errors in double strand break (DSB) repair and replication processes. Genomic instability has important consequences for genomic disorders, neuro-degenerative disease and animal evolution. There are three main aims of this research. 1) Develop stochastic models for the different mechanisms of SV for mation and use Approximate Bayesian Computation (ABC) methods to estimate parameters such as relative contributions and length-dependent mutation rates from published datasets. 2) Test the hypothesis that local genome architecture contributes to genomic instability by using a combination of the developed ABC framework and machine-learning methods to relate variant position and mechanism to genomic features. Use this to predict interesting regions of the genome for further study. 3) Examine the effect of genome instability in complex disease (metabolic, cardiovascular and autoimmune), neurodegenerative disease, population differentiation and evolution through collaborative efforts with geneticists and clinicians using both human and animal sequencing.

Amount: £774,472
Funder: The Wellcome Trust
Recipient: University College London

Cellular and synaptic mechanisms of learning in cortical circuits. 27 Jan 2012

Genetically encoded calcium indicators combined with two-photon imaging enable the repeated measurement of response properties of individual neurons in the cortex of living animals through a cranial window. These indicators are also suitable for repeatedly recording activity at single synaptic inputs in vivo and, when combined with other markers, further allow determining the dynamics of synaptic structures (dendritic spines and axonal boutons). First, I will apply these methods in mouse visua l cortex to follow long-term changes in neuronal responses and associated spine and bouton reorganization, as well as changes in the visual properties of synaptic inputs in the same cells during experience-dependent plasticity induced by repeated episodes of monocular deprivation. This will enable me to relate synaptic rewiring to changes in neuronal response properties, and to determine which synaptic changes may underlie long-term information storage. Second, I will use the same methods to stu dy cortical changes during perceptual learning by training mice in visual discrimination tasks. By relating neuronal response changes to structural and functional synaptic modifications induced by perceptual improvements, I will test if similar mechanisms underlie this form of learning. Together, this work will give insights into the cellular and circuit mechanisms of learning and memory formation.

Amount: £25,000
Funder: The Wellcome Trust
Recipient: University College London

Prostaglandins as potential biomarkers and therapeutic targets in critical illness-associated immune dysfunction. 27 Jun 2012

The host laboratory has demonstrated that prostaglandin E2 (PGE2) impairs the innate immune systems ability to kill bacteria and that plasma levels are elevated in an immunosuppressive state, cirrhosis. Cirrhosis-induced immune paralysis is fully reversed by PGE2 inhibition. Pilot-data has demonstrated that plasma from patients with community-acquired pneumonia (CAP) induced leukocyte dysfunction increasing in severity between day 1-3, resolving thereafter. This was also reversed with PGE2/D2 an tagonists. Nosocomial infections occur in 5% of hospital and 30% of intensive care admissions annually. I hypothesise that PGE2/D2 underlie critical illness associated immune dysfunction, and aim to identify PGs as prognostic biomarkers and potential therapeutic targets to prevent hospital-acquired secondary infection I will carry out comprehensive lipodomic analysis on plasma of patients admitted to UCLH with a primary diagnosis of CAP. Correlation in temporal changes in eicosanoid levels wi th clinical markers and outcomes will be explored, along with in vitro quantification of PGE2 contribution to immune dysfunction. In parallel, I will use murine cecal-ligation and puncture followed by pneumonia challenge to mechanistically dissect the role of PGs in secondary/opportunistic infection at a receptor, cellular and enzyme level acquiring training in flow assisted cell sorting, animal models of acute/resolving inflammation, pharmacology and molecular biology

Amount: £230,705
Funder: The Wellcome Trust
Recipient: University College London

Can we treat genetic blood disorders by transplantation of stem cells to the fetus? 27 Jun 2012

Congenital diseases such as blood disorders are responsible for over a third of all paediatric hospital admissions. In utero transplantation (IUT) could cure affected fetuses but so far in humans, successful IUT has been limited to fetuses with severe immunologic defects. The maternal immune system and a functionally developed fetal immune system are thought to be responsible. This could be overcome by the use of autologous cells. Autologous haematopoietic progenitors can be easily derived from amniotic fluid (AF). They can engraft long term into fetal sheep. IUT of genetically corrected autologous amniotic fluid stem cells (AFSCs) could be therapeutic strategy for the treatment of congenital disease like thalassaemia. Using a novel humanised mouse model of thalassaemia (CA), which closely mirrors human disease, I will study IUT with AFSCs from CA mice after gene correction with a lentivirus vector containing the beta-globin gene. I will first demonstrate engraftment of normal GFP+ mou se AFSCs into CA mutants. Then transplant gene corrected beta-thalassaemia CA mutant mouse AFSCs. The primary outcome measure is neonatal survival of homozygous CA mice. Secondary outcome measures will include stable correction of the severe anaemia. Finally I will study gene transfer to AFSCs from human pregnancies affected by Thalassaemia.

Amount: £91,169
Funder: The Wellcome Trust
Recipient: University College London

Pre-synaptic neurological channelopathies. 27 Jun 2012

Inherited mutations of specific ion channels (channelopathies) are associated with several paroxysmal neurological disorders including migraine, epilepsy and ataxia. At a basic level, channelopathies such as Episodic Ataxia type 1 (EA1) and Familial Hemiplegic Migraine (FHM) provide unique insight into neuronal circuit development, synaptic function and neurotransmitter release. Both EA1 and FHM mouse models have shown increased neurotransmitter release compared to control mice. A potential hypo thesis to account for this is that pre-synaptic action potential shape is altered in these disorders. To test this, direct electrophysiological recording of the most prevalent pre-synaptic boutons is required, a process now possible due to the development of SICM. My aims are a) To identify synaptic boutons in hippocampal neuronal cultures and create high resolution contour images of them using SICM; b) To achieve whole cell patch and measure action potential width from synaptic boutons; c) W ork with the EA1 knock-in (KI) mice and investigate differences in presynaptic action potential width between wild-type and KI mice, and between excitatory and inhibitory synapses; d) Work with the FHM knock-in mice to ascertain whether action potential shape differs between excitatory and inhibitory synapses and explore the impact of any such differences on calcium-dependent neurotransmitter release.

Amount: £192,126
Funder: The Wellcome Trust
Recipient: University College London

Establishing the Role of the FoxG1 transcription factor in normal and glioma-derived neural stem cells. 27 Jun 2012

Glioblastoma (GBM) is the most common and lethal primary brain tumour. GBMs contain a population of cells that display characteristics of neural stem cells. Understanding the action of the lineage specific transcription factors responsible for orchestrating self-renewal in this population and in their normal stem counterparts offers promise in identifying therapeutic targets. Through pilot studies comparing gene expression in normal NS cell cultures with GBM-derived NS (GNS) cells we have ident ified FOXG1 as a brain-specific transcription factor that is consistently overexpressed in GNS cells. Previous studies have implicated FOXG1 in control of cell cycle and differentiation pathways (p21 and Bmi-1). The aim of this project is to define the function and transcriptional targets of FOXG1 in these malignant and non-malignant contexts. I will make use of established and well characterised NS and GNS cell lines as the model system and use intracranial xenotransplantation as an in vivo a ssay of tumour formation. The objectives are: 1) Monitor the changes in FOXG1 mRNA and protein during differentiation. 2) Perform gain-of-function studies using 'tuneable' overexpression. 3) Perform loss-of -function studies using the latest genome editing technologies (TALENs). 4) Define genome-wide transcriptional targets of FOXG1 using chromatin immunoprecipitation and deep sequencing (ChIP-Seq).

Amount: £252,990
Funder: The Wellcome Trust
Recipient: University College London

Investigating the epidemiology of tuberculosis and the cost effectiveness of novel diagnostic screening pathways in migrants to the UK. 29 Mar 2012

BACKGROUND: Tuberculosis is an important global public health problem and migrants to the UK have a disproportionately high burden of disease. AIM: This fellowship aims to investigate the epidemiology of tuberculosis in migrants to the UK; and examine the cost effectiveness of novel diagnostics and screening pathways for migrant tuberculosis control. OBJECTIVES: 1. Describe the epidemiology of tuberculosis in UK migrants, including: 1a. What is the prevalence of active pulmonary disea se in migrants at the time of new entrant screening? 1b. What is the future incidence in individuals without active disease on migration? 1c. What proportion of incident cases of tuberculosis are acquired in the UK? 2. Evaluate what combination of existing and novel diagnostic tests for active and latent tuberculosis would be most cost effective in UK migrants. METHODOLOGY: 1. Retrospective cohort study. Migrant screening, surveillance and strain typing databases will be probabilistic ally matched allowing the calculation of parameters in objective one. 2. A dynamic transmission model will be built to examine the combination of existing and novel diagnostic tests for active and latent tuberculosis that would be most cost effective. OPPORTUNITIES: To provide evidence for screening policy in a vulnerable population with a high burden of tuberculosis.

Amount: £181,967
Funder: The Wellcome Trust
Recipient: University College London

The molecular basis of cytochrome c oxidase deficiency. 06 Mar 2012

Cytochrome c oxidase (COX) is an enzyme required for mitochondrial energy production and COX deficiency accounts for 25% of all cases of mitochondrial disease. COX deficiency may be due to a mutation in mitochondrial or nuclear subunit genes, or nuclear encoded assembly factor genes. The clinical phenotype is heterogeneous, ranging from neurodegenerative disorders to multiorgan failure. Making the diagnosis is difficult and there is no effective treatment. We will examine 45 children with iso lated COX deficiency where the genetic diagnosis is unknown. We will determine the frequency of nuclear encoded COX subunit and assembly factor gene mutations using an integrative genomics approach. We will combine targeted next generation exon sequencing of candidate genes, homozygosity mapping (in consanguineous families), whole exome sequence analysis followed by bioinformatics and functional studies. We will also investigate the effect of drug therapy in human cell cultures with confirmed ge netic COX deficiency. We expect to discover new genetic mutations in this clinically heterogeneous cohort. We will develop high throughput novel techniques which will be translated into the diagnostic laboratory. This will improve diagnosis and facilitate prenatal diagnosis in COX deficiency. Our studies using a candidate drug panel will provide insights into treatment options in COX deficiency.

Amount: £232,545
Funder: The Wellcome Trust
Recipient: University College London