PhD Studentship: Using in vivo and in vitro models of inflammation to develop a new strategy to tre

A person is diagnosed with Chronic Obstructive Pulmonary Disease (COPD) every five minutes. COPD is an umbrella term for diseases such as bronchitis and emphysema and is characterised by ongoing inflammation in the airways. This leads to breathlessness, persistent cough and becomes severely life-limiting. A key element of COPD is the migration of inflammatory leukocytes from the blood into the airways. These cells cause significant damage to the lung tissue and this worsens and perpetuates the disease process.

This progressive and irreversible condition unfortunately has no cure. Our recent research suggests we may have found a new class of drugs to treat patients with COPD. These drugs inhibit a family of receptor tyrosine kinases, and a major advantage is that these well-tolerated, safe medicines are already in clinical use for patients with cancer. Based on pilot experiments we have carried out in the laboratory, we believe they will also prevent inflammation in the airways.

This studenthip will take various models of inflammation and test the ability of these clinical compounds to reduce inflammation. To do this we will isolate isolate inflammatory leukocytes (neutrophils) from the blood of human subjects. We will put these cells in an inflammatory environment, exposing them to factors they encounter in the COPD lung, and will test whether the kinase inhibitors can stop these cells from acting in a pro-inflammatory manner. We will also show the importance of kinases in inflammation in zebrafish larvae by observing how well the larvae are able to heal tissue inflammation. We believe our work will identify a new therapeutic strategy for patients with COPD and other chronic inflammatory diseases.

The techniques and models to be employed in this project are well-established in the Prince and Renshaw laboratories, and therefore full support is available during the training process. The wide variety of both general (tissue culture, flow cytometry, ELISA, microscopy, qPCR) and highly specialised techniques (leukocyte isolation from blood, CRISPR/Cas9 molecular engineering and zebrafish in vivo models of inflammation) will provide an excellent scientific training programme. In addition to practical skills, the student will benefit from an excellent Doctoral Development Programme here at the University of Sheffield, which provides numerous opportunities for wider development.

Funding Notes

The Faculty Scholarships for Medicine, Dentistry & Health cover fees and stipend at Home/EU level. Overseas students may apply but will need to fund the fee differential between Home and Overseas rate from another source.