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PhD Studentship: Establishing a Rationale for FGF23 Modulation as a Therapy in the Critically Ill Patient

University of Birmingham - Institute of Inflammation and Ageing

Qualification Type: PhD
Location: Birmingham
Funding for: UK Students
Funding amount: This 4 year programme is funded by The Lorna & Yuti Chernajovsky Biomedical Research Foundation - the scholarship will cover PhD Stipend (as defined by UKRI), consumables and PhD fees.
Hours: Full Time
Placed On: 22nd May 2020
Closes: 1st September 2020

This PhD Studentship is hosted in the Institute of Inflammation and Ageing at the University of Birmingham within the Queen Elizabeth Hospital Birmingham. Supervision will be provided by Dr Dhruv Parekh (Senior Lecturer in Acute and Critical Care), Professor David Thickett (Professor of Respiratory Medicine) and Dr Aaron Scott (Lecturer in Respiratory Sciences).

Project Outline

Most causes of critical illness involve infection with sepsis, immunosuppression or inflammation secondary to trauma or complications following major surgery. Sepsis is a particularly important cause of critical illness that is increasing in incidence with both bacterial and viral pneumonia as the commonest causes. When a patient becomes critically ill, this adversely affects both the adaptive and innate immune system with significant dysregulation of almost all inflammatory, coagulation, and metabolic pathways. 

In health, fibroblast growth factor 23 (FGF23) is an endocrine hormone mainly produced by osteocytes and osteoblastic cells, which is classically involved in the homeostasis of vitamin D and contributes to regulation of calcium and phosphate. FGF23 also has a wider direct role in the regulation of host innate immune and inflammatory responses. Multiple recent studies suggest that iron deficiency, Hypoxia Inducible Factor (HIF)-1α and systemic inflammation also upregulate FGF23 production. Although there is suggestion of increased mortality, acute kidney injury, myocardial function and infection in acute illness associated with raised FGF23, the role of FGF23 biology has not been extensively studied in patients with acute inflammation in sepsis/critical illness.

Hypothesis:

1) Acute inflammation drives FGF23 release that directly impairs innate immune responses in critical illness/sepsis leading to adverse clinical outcomes.

2) Dysregulated FGF23 leads to vitamin D catabolism in critical illness promoting an exaggerated deficiency, poor response to replacement therapy and counters the effects of vitamin D on inflammation and innate immune responses.

These will be tested utilizing patients recruited to the VITDALIZE Trial, in-vitro cellular studies and murine models.

Our research group is based within the newly built Queen Elizabeth Hospital in a state of the art clinical research/laboratory facility. Working with University Hospitals Birmingham, we have unique access and capacity to recruit and study critically ill patients, with laboratories directly adjacent to the largest dedicated ICU in Europe. Using the skills of our multi-disciplinary team, including basic scientists, doctors, nurses, allied health care professionals and physiologists, we are working together to better understand underlying disease mechanisms. 

The student will receive support from post docs and technicians within the group to help them achieve their goals- our group has a very collaborative ethos. The student will be encouraged to present data at national/international meetings. Students from our lab have been very successful winning prizes at national and international conferences, including; British thoracic society, Europe a thoracic society conference and American thoracic society scientific meeting.

Person Specification

Applicants should have a strong background in laboratory research, and ideally a background in macrophage biology, inflammation and murine studies. They should have a commitment to research in Inflammation biology and hold or realistically expect to obtain at least an Upper Second Class Honours Degree in Medical Sciences or Inflammation or Immunology.

How to apply

For information enquiries and application details, please contact Dr Dhruv Parekh (d.parekh@bham.ac.uk).

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