|Title||Potential for Honours, Masters or PhD Projects|
|Location||Global and Tropical Health, Menzies School of Health Research, Darwin|
Research Area 1: Immunology
Supervisors: Dr Tonia Woodberry & Professor Nicholas Anstey
Research Project Title: Understanding immune function in sepsis patients receiving statin treatment
The tropical “Top End” of Australia has high rates of severe sepsis and septic patients admitted to Royal Darwin Hospital (RDH) ICU have an over-representation of Indigenous and younger patients, and several causative organisms that are rare elsewhere in Australia.
The high prevalence of sepsis and its high mortality despite current treatments mean that more effective adjuvant therapies are needed.“Statins” (HMG CoA reductase inhibitors), commonly used to treat hypercholesterolaemia, have been shown to have multiple effects apart from lipid lowering. These include anti-inflammatory, immunomodulatory, and anticoagulant effects. A large retrospective cohort study (69,168 patients) has shown that those on regular statins have a significantly lower risk of sepsis and death. However, there are no published randomized controlled trials of statins for the prevention or treatment of sepsis.
The immune system plays a central role in the pathogenesis of sepsis. Regardless of the cause of the infection, there are similar symptoms and sequelae in sepsis patients including dysfunctional T cells and widespread apoptosis of lymphocytes. The mechanisms underlying sepsis-related T cell dysfunction are not well
understood. Our research recently described, for the first time, significant reductions in T cell zeta chain expression and T cell dysfunction in sepsis patients.
We now aim to assess the impact of statin therapy in ICU patients with severe sepsis on T cell zeta chain expression and T cell function. Cells have been cyropreserved from RDH patients who participated in a multi-centre stratified prospective, randomised double-blind, placebocontrolled, phase II trial of statins for the prevention or treatment of sepsis.
This unique laboratory based project is suited to a person who has a passion for clinical immunology and a firm understanding or preferably experience with flow cytometry.
Contact: Tonia Woodberry on 08 8922 7918 or Tonia.Woodberry@menzies.edu.au
Research Area 2: Immunology/Infectious Diseases
Supervisors: Dr Gabriela Minigo, Dr Tonia Woodberry
Research Project Title: Understanding regulatory T cell activation in malaria
Immunopathogenic responses in malaria are known to differ between children and adults, and age is a critical determinant of malaria mortality. Regulatory T cells (Tregs) are key regulators of cellular immune responses, including cytokine secretion, and Treg phenotypes change with age. Little is known about differences in Treg activation between children and adults, particularly in response to malaria parasites. It is unclear how Treg activation following a first malaria infection affects the development of anti-malarial immune responses.
This project will address these knowledge gaps through comprehensive comparison of Treg phenotype and function between children and adults before and after exposure to malaria parasites. Using experimental malaria infection of adult human volunteers (in collaboration with Prof James McCarthy, QIMR and Prof
Michael Good, Griffith University) the impact of Treg activation on the quality of immune memory responses will be studied. Results will be compared with responses in clinical disease using samples obtained from patients with malaria at Menzies’ field sites in South-East Asia.
Contact: Gabriela Minigo on 08 8922 7918 or Gabriela.Minigo@menzies.edu.au