- Total grants
- Total funders
- Total recipients
- Earliest award date
- 10 Apr 2001
- Latest award date
- 30 Sep 2018
- Total GBP grants
- Total GBP awarded
- Largest GBP award
- Smallest GBP award
- Total Non-GBP grants
Does 2A-mediated stop codon-independent termination of translation predominateover start codon-independent re-initiation of translation under conditions of translational 'stress' ? 19 Oct 2005
The oligopeptide 2A sequence (just 18aa) mediates a co-translational 'cleavage'. When ribosomes encounter 2A, two outcomes ensue. Either (i) translation terminates in a stop codon-independent manner, or, (ii) translation of a specific (glycyl-prolyl) peptide bond is 'skipped' and translation, in effect, re-initiates to synthesis downstream sequences. We propose that this method of protein biogenesis confers the ability to preferntially translate only one part of an open reading frame under conditinos of translational 'stress'. At latter stages of infection this system could direct the remaining cellular resources into translating sequences upstream of 2A (capsid proteins), rather than those downstream (replication proteins). In this manner, the yeild of progeny virions could be enhanced. '2A-like' sequences are found in a very wide range of pathogens and 2A is used extensively in biomedical and biotechnological applications. Our findings will help interpret the role of 2A-like sequences in these other systems and underpin its use in biotechnology. The key goals of the project are twofold; (i) to build a kinetic scheme of protein biogenesis of TME to determine if more capsid, than replication, proteins are made duringinfection, and (ii) to identify what aspect of the translational machinery is determining the outcome of 2A- mediated 'cleavage'.
The body of research into FMDV is impressive; over 150 complete genome sequences, a map of polyprotein processing, full-length cDNA clones from which virus can be rescued ( infectious copies ), a non-infectious replicon cDNA system, characterisation of the virus receptor, atomic structures of the virus particle, L proteinase and 3D polymerase, characterisation of immune responses with detailed epitope mapping. There still remain, however, substantial and critical gaps in our knowledge as to ho w this virus replicates in two modes; (i) very rapid cell lysis (3-4hrs), or, (ii) establishment of persistent infections. Even a cursory inspection of the FMDV genome reveals a number of features which are unique to aphthoviruses. Surprisingly, perhaps, the function or contribution to RNA replication of these features is not understood and is not currently being investigated. Our proposed program of research focuses upon questions concerning the replication of virus RNA and the molecular interactions between virus RNA/virus proteins with host-cell proteins using the (non-infectious) FMD replicon system. An essential element of this proposal is to harness the knowledge gained for the design of new, recombinant, forms of the genome to produce attenuated phenotypes: candidates for a new form of disease control live, attenuated, vaccines.
We will build an E. coli that can detect and kill S. aureus. The project will consist of three steps (Fig 2): detection, destruction, and enhancement. First, we will build E. coli to signal detection of AlP by producing green fluorescent protein (GFP). We will use the BioBrick BBa_1746220 created by Cambridge in 2007 to detect group I AlP in E. coli; Cambridge did not succeed in verifying this BioBrick (igem.org), thus we will first "debug" it to create a working copy. In particular, we note that BBa_l746220 does not include SarA, a general transcription factor believed to act in concert with AgrA to activate promoters P2 and P3 (Novick 2003). We will explore addition of SarA to the BioBrick, as well as other refinements, such as including the entire P2 to P3 promoter regions (Novick 2003). We will pair this with GFP (BioBrick BBa_K203103) to cause fluorescence upon detection of AlP. We will then create our S. aureus destroying E. coli by replacing the GFP with the "Kamikaze" BioBrick BBa_K284022 created by UNICAMP-Brazil in 2009: BBa_K284022 creates lysosyme, thus killing the cell and any nearby bacteria, and has been verified to work (iGem. org). Finally, we will enhance the sensitivity of both these constructs by inserting an E. coli quorum sensing loop in between the AlP detector and the output (e.g. verified BioBrick BBa_l15030, UT Austin 2005): this serves to amplify the signal from AlP to produce greater output (GFP or lysosyme) per cell and recruit other nearby E. coli.
SFX: A UK/European user consortium for a serial femtosecond crystallography beamline at the European X-ray Free Electron Laser. 10 Oct 2013
Third generation synchrotron sources have revolutionised our understanding of the macromolecular machinery of the cell - over 33,000 structures have been elucidated in the last five years, providing atomic detail of macromolecular complexes, membrane proteins and viruses. Fourth generation light sources, such as hard X-ray Free Electron Lasers (XFELs) will allow us to greatly improve one of the bottlenecks of Structural Biology by removing the need for large crystals, which is achieved by outrun ning radiation damage. XFELs also enable sub-picosecond time-resolved analyses and may ultimately provide atomic information for single particles such as viruses and large complexes. The UK is currently not committed to or involved in the construction of a fourth generation light source, including the European XFEL, under construction in Hamburg. This proposal aims to enfranchise the UK structural biology community, amongst the leading in Europe, in this potentially game-changing technology. W e propose to provide training and infrastructure and to directly contribute to the construction and operation of SFX, a user facility for serial femtosecond crystallography at XFEL. An UK Hub at Diamond will allow sample preparation and triage to optimise the use of SFX by UK scientists and maximise the impact of XFEL.
The Bunyaviridae family are a diverse group of over 350 RNA viruses classified into five genera, namely Hantavirus, Orthobunyavirus, Phlebovirus, Nairovirus and Tospovirus. Many bunyaviruses are important pathogens of humans, animals and plants for which preventative or therapeutic treatments are unavailable. Bunyavirus pathogenesis depends on formation of the ribonucleoprotein (RNP) complex, in which the bunyavirus genome is entirely encapsidated by the virus-encoded nucleocapsid protein (N). O nly in the form of the RNP is the genome replicated, transcribed and packaged into new progeny particles. Using Bunyamwera orthobunyavirus and Rift Valley fever phlebovirus, we propose to perform a detailed quantitative analysis of the role of individual N protein amino acids in both gene expression and virus assembly. Critical to these analyses, we have generated the first high-resolution crystal structure of a complete bunyavirus N protein. We will pair this information with findings of our fu nctional analyses to reveal the structure-function relationship of the entire RNP complex for both viruses. Also critically, we will generate infectious viruses incorporating N protein mutations, which will allow us to validate our findings in the context of a live-virus infection, and relate how perturbation of molecular interactions between individual viral components affects the overall viral life-cycle
Towards a worker for the North East to recruit older volunteers.
LifeLines 20 Apr 2016
This is the expansion of a project supporting volunteers aged 50 plus to run activities for vulnerable older people to improve health and well-being. These have previously included art classes, creative writing, yoga and computer club. The group will expand across the city, recruiting more volunteers, supporting more than 800 new people and establishing a Menâ€™s Network to encourage older men to socialise regularly. It will also extend its HealthLink scheme to help older people get to medical appointments.
Young Voices is a three year project that will develop and deliver a creative and engaging programme of volunteering opportunities for young people to enable them to build skills and confidence in a key community environment, that of their local library. CSV will work in partnership with Halton, Manchester, and Oldham Library Services to develop this project.
Community Healthy Living Advisor Volunteers 22 Jun 2006
The Manchester branch of Community Service Volunteers runs a range of projects that encourage people to take up learning via its Media Clubhouse. With this award it will deliver workshops, led by a qualified nutritionist, aimed at individuals who want to become volunteer healthy living advisors. The volunteers will be recruited from groups with multiple disadvantages as well as minority groups based in and around the City Centre.
Volunteer Britain 14 Jul 2005
Community Service Volunteers (CSV) works to reconnect people to their community through volunteering and training and to enrich people?s lives. This project will produce short audio and visual clips on volunteer's experiences, produced by the volunteers themselves. CSV will showcase the clips in order to recognise their efforts and promote volunteering to others, through radio, TV and at local community events. This will be done in conjunction with the 'Year of the Volunteer' campaign.
Older people volunteering at primary schools 11 Jan 2005
The project will empower older people to take an active part in their communities by giving them the opportunity to take the lead in designing and delivering voluntary services to support the development of children in Hackney and Tower Hamlets. Older volunteers will work in primary schools to provide support for pupils, especially those for whom English is an additional language.
CSV 15 Apr 2009
This organisation will set up a new sustainability initiative, creating a website for schools and their communities in the highlands to share experiences. The website will focus on eco projects, learning new ways to live sustainably, preserving energy and actioning change. The grant will be used to pay for website design, event staff costs, catering and volunteer expenses.
This project works with parents and children aged 12-16 to help parents engage with and understand youth sub-culture through multimedia activities including film, radio, multi-media, music and arts projects. Issues of identity and behaviour will be explored by using 'Life Story' books, video diaries and talking families through a journey of their heritage.