PhD in Pharmacy and Pharmaceutical Sciences: Investigating the biomolecular interactions between innate blood defense systems: Complement and coagulation
|Application deadline||19 May 2017|
|Start date||1 October 2017|
|Level of study||Postgraduate research|
|Award type||PhD studentship|
|Number of studentships||1|
Co-ordinated dysregulation of the innate immune response and the coagulation system drives a diverse array of disease types, including sepsis, myocardial infarction, and atypical hemolytic uremic syndrome.
Complement and coagulation are both blood-based proteolytic cascades and integral defence mechanisms that typically protect against pathogen invasion and bleeding.
Although they have distinct functions, complement and coagulation share many structural motifs, are evolutionary linked and several points of cross-talk between each pathway has been recently identified.
However, the mechanisms by which these systems co-operate to maintain health and their role in disease pathogenesis, when dysregulated, is still incompletely understood.
Our group have recently characterised one aspect of this cross-talk, which occurs between thrombomodulin and factor H. We found that the anticoagulant thrombomodulin has moderate complement regulatory activity that is both factor H-dependent and independent (Heurich et al 2016).
Thrombomodulin polymorphisms and mutations have been associated with a number of diseases, one of which is complement-mediated atypical hemolytic uremic syndrome, where an impaired thrombomodulin-factor H interaction contributes to disease pathology (Delvaeye et al. 2009).
The primary objective of this study is to characterise the structure-function relationship of recombinant thrombomodulin mutants with complement proteins and determine their impact on regulating coagulation and complement pathways.
You will be based in the laboratory of Dr Meike Heurich at the School of Pharmacy and Pharmaceutical Sciences. In addition, you will travel to and study at the laboratory of Dr Roger Preston (co-supervisor, Royal College of Surgeons, Dublin).
The research team will provide all necessary training in the requisite techniques, including mammalian cell culture, site-directed mutagenesis, receptor-ligand modelling, protein purification, FPLC, BIACore surface plasmon resonance and coagulation and complement assays.
|Tuition fee support||Full UK/EU tuition fees|
|Maintenance stipend||Doctoral stipend matching UK Research Council National Minimum|
|Residency||UK Research Council eligibility conditions apply|
You should be enthusiastic, driven and willing to work as part of an ambitious, but supportive multidisciplinary research team. You should possess a minimum first class or upper second class honours degree in a biochemistry/genetics/molecular biology-related subject.
Consideration is automatic upon application for admission to the Doctor of Philosophy in Pharmacy and Pharmaceutical Sciences (start date of October 2017).
In the funding section of your application, please select 'I will be applying for a scholarship/grant' and specify that you are applying for advertised funding from the School. In the research proposal section, include the project description contained here.
We reserve the right to close applications early should sufficient applications be received.