Supervisors:
\nPr Daniel Aeschlimann – AeschlimannDP@cardiff.ac.uk
\nMatrix Biology & Tissue Repair Research Unit, School of Dentistry, Cardiff University, Cardiff
\nDr Arwyn Jones – jonesAT@cf.ac.uk
\nDrug delivery and Microbiology Group, School of Pharmacy, Cardiff University, Cardiff.<\/p>\n
Diagnostic assays based on biomarkers of disease are an important tool in patient diagnosis and stratification for treatment as well as evaluation of disease progression and treatment efficacy. Very few indicators for arthritis are currently available to inform the clinician. The overarching aim of this project is to establish sensitive and robust immunoassays for detection of novel epitopes generated as a consequence of aberrant mechanical loading, inflammation and tissue repair responses and evaluate their potential in longitudinal assessment of disease progression in osteoarthritis patients.<\/p>\n
There is substantial evidence that post-translational modifications of proteins, particularly in joint tissues, are directly linked to disease processes. Disease-specific protein modifications may therefore provide a sensitive indicator of disease, as exemplified by citrullinated peptides in rheumatoid arthritis and deamidated gliadin peptides in celiac disease (1,2). Changes in postranslational modifications of proteins are linked to altered intracellular protein trafficking and less frequently, to aberrant extracellular enzymatic reactions (3). This PhD project will investigate the regulation of protein export\/endocytic recirculation with an emphasis on identification of qualitative alterations that are unique to degenerative joint pathologies, and on gaining a molecular understanding of the role of such protein modifications in disease development and progression.<\/p>\n
The successful applicant will join an international team of researchers in a Center of Excellence for Arthritis Research and have access to state-of\u2013the art technology to address research questions and long-standing expertise in research translation.<\/p>\n
1. Hadjivassiliouu et al., 2010. Lancet Neurol 9, 318-330
\n2. Thomas et al., 2013. Amino Acids 44, 161-177
\n3. Al Soraj, et al., 2012. J. Control Release 161, 132-41<\/p>\n