Job Profile Core job information

Job Title PhD Studentship (Marie Curie Early Stage Researcher)

Dept./School/Inst. William Harvey Research Institute Section/Centre/Unit Centre for Biochemical (WHRI/SMD) Pharmacology

Career Family Academic & Education Grade Off-scale (Research)

Working hours per Full time (37.5 hours per week) Appointment 3 years (36 months) week period

Reports to (job title) Professor of Current location Charterhouse Square Immunopharmacology Dean of Research at SMD

Job purpose

To contribute to research investigations in collaboration with and under the supervision of Prof. Mauro Perretti in order to realise the objectives and development of the Marie Curie European Innovative Training Network EVOluTION (European Vascular Interventions and Therapeutic Innovation Network). The science of EVOluTION evolves around the innovative concept of boosting natural protective mechanisms operating in our body, focusing on the vasculature, to answer 3 key questions: Can we exploit mediators and targets of endogenous tissue protection? Can we exploit these pathways to yield innovative therapeutic strategies? Can dietary approaches boost these endogenous protective processes? EVOluTION is an interdisciplinary, inter-sectorial, and international consortium involving 5 leading academic institutions and 1 SME, together with 6 Pharma and biotech companies, 1 Policy-maker, and 1 Patent & Trade firm, from 6 countries. It is expected that the role-holder will engage in network-wide training events, public engagement activities and international collaboration through secondments, at industrial or academic partner institutions within the UK and EU. Objectives of the PhD position The PhD position title is “Microparticles as natural nanomedicines to control vascular reactivity”. Microparticles are extracellular vesicles abundantly present in blood, bearing markers that identify the cell of origin (e.g. endothelial, neutrophil, monocyte, platelet). The concept of microparticle heterogeneity is emerging, whereby the same cell can produce microparticles with distinct components in relation to the mode of activation. The objective is to study human monocyte-derived microparticles in vitro mimicking events that occur in the inflamed vasculature. The role-holder will: 1) produce and characterise by ImageX™ cytometry, Nanoparticle Tracking Analysis (Nanosight™) and sorting monocyte- derived microparticle markers upon application of distinct stimulants [Fc receptor ligation; LTB4 and CCL2], 2) study dynamics of monocyte microparticle generation upon addition of activated platelets (with ADP or thromboxane receptor agonist), and 3) test the functions of microparticles when applied to endothelial cells under flow or to assays of platelet activation. Finally, s/he will 4) search for identified new subsets of monocyte microparticles in plasma samples of mice prone to atherosclerosis and vascular calcification. Expected results of the PhD research project The role-holder will identify subsets of monocyte-derived microparticles and establish their composition as well as their biology in assays relevant to vascular inflammation. Pinpoint subsets to be developed as autologous nanomedicines. Secondments for the PhD research project The role-holder will be seconded by University of Maastricht (2 months) to optimise separation assays with beads loaded with specific antibody, by MosaMedix (Maastricht) (1 month) to be trained on patent writing and filing to protect and benefit from inventions, and by UCD (Dublin) to perform proteomics of specific subsets of microparticles. Requirements Applicants will be considered on an equal basis, subject to the relevant permission to work in the UK as defined by the requirements set out by the UK Border and Immigration Agency. Please visit http://www.ukba.homeoffice.gov.uk/ for more information. Please note there are strict *eligibility requirements* which apply to all Marie Skłodowska-Curie Early Stage Researchers. At the time of the appointment: Applicants must not have resided or carried out his/her main activity (work, studies, etc.) in the UK for more than 12 Organizational chart: