Investigating IL-33 signalling in type 2 innate lymphoid cells (360G-Wellcome-105309_Z_14_Z)

£151,392

Alpha-1 antitrypsin (AAT) is an antiprotease synthesised in the liver, which regulates the proteolytic effects of neutrophil elastase within the lung. Mutations in the SERPINA1 gene cause AAT deficiency, characterised by the polymerisation of AAT and its subsequent retention in hepatocytes, along with a deficiency of circulating AA T. As a result, patients suffer from liver cirrhosis and emphysema. This project aims to develop a diagnostic tool for the non-invasive imaging of AA T polymers within individuals with AA T deficiency and a therapeutic agent to block polymerisation of AAT. The basis for these tools are the polymer-specific 2C1 and polymer-blocking 4812 monoclonal antibodies, respectively. The antibodies will be modified with a disulphide-bridging conjugation molecule, synthesised from starting compounds, and cell-penetrating peptides attached by click chemistry to allow cellular entry. Their internalisation and effect on AAT turnover will be characterised using two models of Z-AAT deficiency and confocal microscopy. The optimum 2C1-conjugate will be subjected to crystallography.

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Grant Details

Amount Awarded 151392
Applicant Surname Petrova
Approval Committee PhD Studentships
Award Date 2014-06-23T00:00:00+00:00
Financial Year 2013/14
Grant Programme: Title PhD Studentship (Basic)
Internal ID 105309/Z/14/Z
Lead Applicant Miss Tsvetana Petrova
Partnership Value 151392
Planned Dates: End Date 2018-08-31T00:00:00+00:00
Planned Dates: Start Date 2014-09-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Scotland
Sponsor(s) Prof Simon Arthur, Prof Tom Owen-Hughes