Field: Critical care - sepsis, inflammation

Location: St Lucia campus, Lady Cilento Children's Hospital

Type of student: M Phil or PhD – intercalated within MD program

Type of work: Clinical research in the PICU and Lady Cilento Children’s Hospital, Wet lab (molecular and cellular biology), Animal model of sepsis/SIRS

Brief synopsis:

Our vascular leak group is a collaboration between and A/Prof Trent Woodruff's in the School of Biomedical Sciences, UQ, and A/Prof Mark Coulthard at the Lady Cilento Children’s Hospital. We are aiming to discover novel therapies for life threatening and severe sepsis/systemic inflammatory response syndrome.  There are approximately 10,000 children admitted to intensive care units in Australia and New Zealand each year and nearly 500 have severe sepsis and 50 will die from their disease. On a worldwide scale severe infections is estimated as the fifth commonest cause of death (after heart diseases, cancers and stroke) and in the developing world is a major cause of illness and death. 

 

Our hypothesis is that Eph/ephrin signalling is fundamental to the pathogenesis of vascular leak in severe sepsis/systemic inflammation by driving changes in the vascular endothelial phenotype. We have a novel therapy which abrogates vascular leak in a animal models of systemic inflammation. We now need to test this drug approach in a model of infection-induced severe sepsis. In addition to mouse experiments, we are also testing microdialysis and plasma levels endothelial activation markers as a method of monitoring vascular endothelial integrity in children undergoing cardiac surgery for repair of congenital heart disorders and critically-ill children admitted with sepsis. Our in vitro experiments are also designed to investigate the endothelial signalling pathways driven by Eph/ephrin interaction. In summary, we are developing an innovative method of monitoring vascular endothelial integrity and we have a novel therapy for sepsis, which focuses on restoring the integrity of the vascular endothelium, which is the final common pathway for sepsis.

 

This research project has a broad scope and will give the student a wide range of opportunities to undertake clinical research, learn molecular, cellular and animal model techniques. It is ideally suited to a student who is considering entering a critical care or surgical training program in future and will prepare the student for the physician-scientist pathway following graduation. The project is supported by a grant from the Financial Markets Foundation for Children and NHMRC project grant (APP1142995) commencing in 2018.

Prerequisite skills:  Science degree with Honours, Laboratory experience helpful but not essential

Time frame: January 2019

Example Publications:

Woodruff TM, Wu MC, Morgan M, Bain NT, Jeanes A, Lipman J, Ting MJ, Boyd AW, Taylor SM, Coulthard MG. EphA4-Fc Treatment Reduces Ischemia/Reperfusion-Induced Intestinal Injury By Inhibiting Vascular Permeability. Shock. 2016 Feb;45(2):184-91.

Coulthard MG, Morgan M, Woodruff TM, Arumugam TV, Taylor SM, Carpenter TC, Lackmann M, Boyd AW. Eph/Ephrin signaling in injury and inflammation. Am J Pathol. 2012 Nov;181(5):1493-503.

Supervisors

Associate Professor Mark Coulthard

Head, Discipline of Paediatrics and Child Health

A/Prof Trent Woodruff

NHMRC Career Development Fellow
School of Biomedical Sciences, Faculty of Medicine