Applications are invited for a Senior Post-Doctoral Fellow in the Haemostasis Research Laboratory led by Prof. James O'Donnell and located in RCSl. The research group is an international group, with a strong publication record. Our research focus is in defining the physiological and pathological importance of a series of different coagulation glycoproteins, including von Willebrand factor, procoagulant Factor VIII and anticoagulant protein C.
Severe Plasmodium falciparum malaria is responsible for more than 1 million deaths per annum. The majority of these deaths occur in children under the age of 5 years in sub-Saharan Africa. In spite of this significant mortality, the molecular mechanisms involved in the pathophysiology of P. falciparum remain poorly understood. However, sequestration of P. falciparum-infected erythrocytes (IE) in the microvasculature of vital organs, particularly the brain, plays a key role in this process. Previous studies have demonstrated that sequestration involves adhesion of IE to endothelial cell (EC) surfaces. A number of specific receptors expressed on EC surfaces are important in regulating IE adhesion (e.g. CD36). Expression of these receptors varies significantly between different vascular beds, and can be regulated in response to inflammatory cytokines (e.g. TNF and interleukin-1).
Von Willebrand factor (VWF) is a large plasma glycoprotein that plays a critical role in haemostasis by mediating the adhesion of platelets to sites of vascular injury. Plasma VWF is derived entirely from biosynthesis within EC. We have previously reported that plasma VWF levels are markedly elevated in children with severe P. falciparum infection, consistent with acute EC activation (Hollestelle MJ et al. Brit J Haematol 2006; 133: 562-9). Furthermore, we have also shown that this increase in VWF is not merely a marker of EC activation (Larkin D et al, PLoS Pathogens 2009; 5(3) e1000349). Rather, we have demonstrated an entirely novel role for VWF playing a critical role in mediating the adhesion of P. falciparum IE to activated EC surfaces (Bridges D et al, Blood, 2010; 115(7):1472-1474; O'Regan et al, Blood 2016; 127(9):1192-1201).
The current project will build upon our previous work in this field to investigate how VWF influences the pathogenesis underlying cerebral malaria, and determine whether VWF-targeted therapies can improve outcome in children with severe malaria infection.
The successful applicants will join an established group of five post-doctoral fellows and three PhD students already working in this area, and will use a wide range of molecular and cell biology techniques during the course of this project. The position is funded for 3 years.
The applicant should have a strong research record including publications (relative to career stage), and be highly motivated and dynamic. Good communication and interpersonal skills are required, as well as an ability to work with a multidisciplinary team. We are looking for someone to start the position as soon as possible.
Applicants should have a PhD in Molecular Biology/Biochemistry/Genetics or related biological subject. Experience in the area of haemostasis, immunology, vascular biology would be advantageous, but not essential. Applicants with experience of current molecular biology techniques, protein biochemistry and mouse models of disease are particularly encouraged to apply. The ideal candidate would be self-motivated, creative and highly competent, as evidenced by first author publications in recognised journals.