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Quantifying the development of neural progenitor polarisation 27 Apr 2017

Apicobasal polarity plays a fundamental role in the defining functional features of neural progenitors during the early stages of embryonic development. The apical pole in neural progenitors is specialized for multiple rounds of progenitor divisions, resulting in brain growth, where as the basal pole forms the environment where neuronal differentiation will occur. However, it is not well understood how the apicobasal polarity of neural progenitors is established. During the project, we will test a hypothesis which suggests that apicobasal polarity is progressively generated and can be monitored by quantifying a Cdh2 protein gradient along the apicobasal axis in neural progenitors. A key goal will be to determine the distribution of the Cdh2 protein over time during neural progenitor polarization. To do this we will make three-dimensional time-lapse movies of developing neural primordium in zebrafish embryos that express a transgene Cdh2-GFP. The transgene containing GFP will make it possible to visualize the distribution of the Cdh2-protein during progenitor polarization. Quantification will be done using FIJI image analysis software.

Amount: £0
Funder: The Wellcome Trust
Recipient: King's College London

Quest Consultancy Day for Pyle Swimming Pool 23 Jan 2014

Funding under Sport England's NBS Quest funding programme for a Revenue project titled 'Quest Consultancy Day for Pyle Swimming Pool'. This project lists its main activity as Association Football.

Amount: £450
Funder: Sport England
Recipient: Halo Leisure
Region: West Midlands
District: County of Herefordshire

Purchase of Modular Units at Simpson and Jericho Lane 03 Mar 2016

Funding under Sport England's Parklife funding programme for a Capital project titled 'Purchase of Modular Units at Simpson and Jericho Lane'. This project lists its main activity as Association Football. This funding has contributed towards a Artificial Grass Pitch - Artificial Grass Pitch (Rubber Crumb Pile (3G))

Amount: £0
Funder: Sport England
Recipient: Liverpool City Council

Camp 2017 01 Aug 2017

As part of our annual program we provide an 8 day adventure holiday. For some this is their only time away from home. This is provided at very low cost to those attending, to ensure that no one is excluded and heavily subsidised by fund raising activities. We plan and provide as many of the activities as we can in-house so as to keep the costs to a minimum. Some of the more challenging activities however require specialist leadership that goes beyond the skills that we currently have. The week away helps young people to understand the need to routine and self discipline in life. Activities are both challenging and of interest. During the week the young people will visit Haytor Rock, undertake a trek across the moor, visit a conservation centre, bush craft, an activity day with balance beam, Pampa Pole, Rock climbing, swimming, multi sports and challenges. The activities program is designed to provide challenging situations that help the young person develop in confidence. Pushing young people beyond where they would normally be. This year we are wanting to provide for a day session of Beams & Pampa Pole in the morning and Rock Climbing. Balance Beams This is a treetop favourites, participants walk along horizontal telegraph poles set high up in the trees. The key word in the last sentence is definitely ‘high’ but they will be secured by a rope and harness controlled by the rest of their group! Pampa Pole This activity is anything but pampering… participants climb to the top of a pole while attached to a rope then jump off and attempt to touch a swinging ball. This looks easy when their feet are on the ground… Rock Climbing/Abseiling Dartmoor is a wonderful place for groups to try climbing. Many of the granite tors scattered across Dartmoor offer a range of routes, including some challenging ones but we also offer various opportunities for learning the basic skills of climbing. Due to the location on the edge of Dartmoor we are spoilt for choice with several popular rock climbing locations all within half an hour’s drive. For introductory climbing sessions we will use Leigh Tor, Dewerstone or Chudleigh.

A study of the interactions between proteins involved in chromosome segregation in Bacillus subtilis using the yeast-two-hybrid system 27 Apr 2017

During sporulation in the bacterium Bacillus subtilis, one of the sister chromosomes is translocated into the developing prespore. This mechanism is a useful model for studying chromosome segregation, a process which is vital in all organisms. The exact mechanism of chromosome segregation in sporulating B. subtilis is not fully understood. A protein complex, involving many proteins including Soj, Spo0J, MinD, MinJ, RacA, ComN and DivIVA, is known to anchor the origins of the sister chromosomes at opposite cell poles. We propose to test the direct interactions between members of this protein complex using yeast-two-hybrid assays. To begin with we will test interactions between the proteins Soj, Spo0J and MinD. Each of these are known to form dimers, and results from genetic and cell biology studies show that interactions between Soj-Spo0J and Soj-MinD are important for the anchoring of the chromosome origins to the cell poles. These latter interactions have not been shown directly and we aim to test these in this project. The project will hopefully move on to test further protein interactions in the complex, including those with RacA and ComN. Any interactions observed between these proteins will further our understanding of chromosome segregation in B. subtilis.

Amount: £0
Funder: The Wellcome Trust
Recipient: Newcastle University

Organisation of pericentromeric chromatin in Saccharomyces cerevisiae 31 Jan 2017

Successful cell division relies on faithful chromosome segregation. Central to this process is sister chromatid cohesion by cohesin that topologically entraps sister chromatids. Cohesin shows increased association with chromosomal regions surrounding the centromere, called pericentromeres. Pericentromeric cohesin is crucial during both meiosis and mitosis. In meiosis I, when homologous chromosomes segregate, pericentromeric cohesion is protected from separase-dependent cleavage ensuring that sister chromatids stay together until they segregate in meiosis II. In mitosis and meiosis II, pericentromeric cohesin facilitates chromosome biorientation by establishing preferred kinetochore geometry for capture by microtubules. How exactly pericentromeric cohesion facilitates chromosome biorientation is unknown. It was proposed that pericentromeric cohesin establishes intramolecular linkages allowing the pericentromere to adopt a cruciform structure. This would facilitate a back-to-back geometry of kinetochores and would promote kinetochore capture by microtubules from opposite spindle poles. This project aims to characterise the conformation of the pericentromere in budding yeast. I will examine how the conformation of pericentromeric chromatin responds to the presence and absence of tension that is exerted on chromosomes during biorientation. The research will extend to mitotic and meiotic cells, with wild type and cohesin-deficient backgrounds. Ultimately, this will further our understanding on how kinetochore geometry facilitates accurate chromosome segregation.

Amount: £0
Funder: The Wellcome Trust
Recipient: University of Edinburgh

Rate of degradation of Aurora kinases 27 Apr 2017

Aurora kinases regulate the segregation of chromatids and are key enzymes in mitosis. AurA assembles the spindle poles; AurB faciliates cytokinesis of the daughter cells. Their ubiquitin-mediated degradation regulates the transition from mitosis back to interphase and show different kinetic profiles: AurA degrades 5-fold faster than AurB. Previous unpublished data from the Lindon lab showed that a AurA1-133-AurB78-345 chimera tagged with GFP degraded with similar kinetics to full-length AurA. Therefore all of the information required for rapid degradation of AurA resides in the 1-133 region. We plan to construct various AurA-AurB chimeras and express them in dividing cells. We will carry out a quantitative analysis of degradation of these chimeras using single-cell fluorescence timelapse assays. We aim to identify the the minimal sequence within AurA1-133 required to specify accelerated degradation kinetics. We plan to compare this with other known regulatory sequences for ubiquitin-mediated degradation ('degrons') and to gain a better understanding of how AurA engages the destruction machinery to affect its degradation kinetics. This information can assist the design of new therapeutic tools, such as PROTACs, that harness ubiquitin-mediated degradation to destroy targets not druggable by conventional means.

Amount: £0
Funder: The Wellcome Trust
Recipient: University of Cambridge

Probing the role of outer membrane transport processes in host-­pathogen interactions using computational and single-­molecule biophysical approaches. 31 Jan 2017

The outer membrane (OM) of Gram-negative bacteria is a significant protective barrier. It is composed of an inner leaflet of phospholipids and an outer of lipopolysaccharide (LPS) with OM proteins (OMPs) that span the membrane. Recently OMPs have been shown to be inserted at discrete and non-uniform locations across the membrane, where they remain due to restricted lateral diffusion. These ‘islands’ are pushed to the poles by cell growth, with new material inserted at mid-cell. OM turnover during bacterial growth may have a role in immune system evasion. One key mechanism regulating human immune responses is the assembly of complement components on the OM nucleated by immunoglobulin binding. This process can lead to lysis of bacteria through insertion of pore complexes in the OM. Complex formation depends on localised clustering of antibodies, which is constrained by the location and molecular diffusion of antigens in the OM. In this project we will use computational and single-cell biophysical techniques to test our hypothesis that spatial confinement of LPS and OMPs near their insertion sites influences activation of the antibody-mediated complement pathway. We will test our hypothesis in Escherichia coli and Salmonella typhimurium, where immune evasion has a key role in pathogenesis.

Amount: £0
Funder: The Wellcome Trust
Recipient: University of York