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Novel regulatory pathways leading to Neutrophil Activation

School of Medicine, Dentistry and Biomedical Sciences | PHD

Applications are now CLOSED
Funding
Funded
Reference Number
SMED-2241-1022
Application Deadline
17 April 2024
Start Date
1 October 2024

Overview

In chronic lung diseases such as Cystic Fibrosis lung disease or Chronic Obstructive Pulmonary Disease, the lung is susceptible to destruction of lung tissue by human cells that normally participate in removing bacteria from the lung. These human cells (neutrophils) release enzymes that can degrade lung tissue and cause inflammation in the lung. In this study, we will evaluate how these enzymes are synthesised prior to their release from neutrophils which will include development of new inhibitors to regulate their activity

Neutrophil Serine Proteases (NSPs) such as Neutrophil Elastase (NE) are known to be present in the lungs of individuals with various chronic lung diseases including Cystic Fibrosis (CF) lung disease and Chronic Obstructive Pulmonary Disease (COPD). It is known that NE correlates significantly to the development of bronchiectasis in early CF and other studies have demonstrated that inhibition of another protease, cathepsin C (CatC), which is known to regulate NSP activation, results in reduced frequency of exacerbation in individuals with bronchiectasis. However, recent data from the Taggart laboratory shows that there is another level of regulation of NSP activity. The proposed project will delineate further this novel NSP processing activity and evaluate how this activity impacts neutrophil function including oxidant generation and bacterial killing. In addition, there will be a focus on measurement of protease activity assays and analysis of neutrophil gene expression. The study will be a collaboration between the Taggart laboratory in the Wellcome Wolfson Institute for Experimental Medicine, the Williams laboratory in the Patrick G Johnston Centre for Cancer Research, the Tirouvanziam laboratory in the Emory University, Atlanta, USA and the company partner ProAxsis, where the student will spend time conducting protease activity assays

Funding Information

Funded by the Department for the Economy (DfE). For UK domiciled students the value of an award includes the cost of approved tuition fees and maintenance support the 2024/25 rates are still to be confirmed (current rates for 2023/24 are Fees £4,712, Stipend £18,622). To be considered eligible you must have been ordinarily resident in the UK for the full 3-year period prior to the start of the studentship and you must be ordinarily resident in Northern Ireland on the first day of the start of the studentship. For further information about eligibility criteria please refer to the DfE Postgraduate Studentship Terms and Conditions at https://www.economy-ni.gov.uk/publications/student-finance-postgraduate-studentships-terms-and-conditions

Project Summary
Supervisor

Professor Cliff Taggart

More Information

askmhls@qub.ac.uk

Research Profile


Mode of Study

Full-time: 3 Years


Funding Body
DfE
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