PhD Project
Investigation of Multiple Myeloma plasma Extracellular Vesicle (EV) biomarker
signature as non-invasive liquid biopsy for diagnosis and monitoring.
PI: (opens in a new window)Assoc Prof Margaret McGee
Background: Multiple myeloma (MM) is an incurable malignancy characterised by monoclonal expansion of plasma cells in the bone marrow and it is the second most common haematological malignancy worldwide. Current treatment regimens consist of autologous stem cell transplant and/or 3- and 4-drug regimens and despite improved treatments, therapy is not curative and all patients ultimately relapse. Typically, the trajectory of MM is characterized by a pattern of recurrent remissions and relapses, with patients becoming increasingly refractory to treatment. A major unmet need is non-invasive effective predictors of MM disease stage and therapy response that will inform clinical decisions and improve patient outcomes.
Extracellular Vesicles (EVs) represent promising non-invasive biomarkers as they are membrane enclosed nanoparticles containing protein, RNA and DNA that are secreted by the tumour cells and as a result have multiple potential biomarkers protected within a singlevesicle. These properties have brought EVs to the forefront as robust, next-generation content-rich cancer diagnostic modality. In support of that, a large number of clinical trials involving EVs are currently underway (www.clinicaltrials.gov) and Bio-Techne's ExoDx Prostate (IntelliScore) (EPI) test is the first EV diagnostic assay to get FDA approval in 2019 to stratify prostate cancer risk for biopsy.
The Mc Gee lab adopts multi-omic approaches to characterise peripheral blood and bone marrow EVs from MM patients for insight into disease mechanisms of action (MoA) and biomarker discovery. They have provided proof-of-principle that peripheral blood EVs represent easily accessible biomarker of MM therapy resistance (DOI10.3390/cells11213365) and have developed biomarker signatures that correlate with disease (DOI:10.3390/cancers16051011 and unpublished). The objective of this project is to exploit EV biomarkers for MoA studies and as a non-invasive approach for diagnosis and monitoring, which currently relies on an invasive bone marrow examination. This will involve (1) Application of Artificial Intelligence tools to interrogate existing EV protein and RNAseq datasets, (2) Investigation of novel disease MoA and, (3) Development and validation of clinically relevant biomarker assays. The results from this project will be better understanding of MM progression and the translational development of a non-invasive blood test for diagnosis and monitoring.
We seek one motivated and enthusiastic PhD candidate to work on this exciting project with the ultimate goal of supporting the implementation of precision oncology. The PhD candidate will receive training in a range of dry and wet lab techniques including AI data analysis and integration, EV isolation and characterisation, protein and RNA assay development using multi-colour flow cytometry, multiplex ELISA and digital PCR. In addition, the PhD candidate will liaise with clinical colleagues at the Mater hospital for sample collection. They will also have the opportunity to undertake research exchange visits to EV research groups across Europe.
Requirements: EU and/or UK candidates should have a BSc (First class or 2.1 Honours) and/or MSc in Biochemistry, Molecular Biology, Biomedical Sciences or related discipline. Candidates should be prepared to work in a collaborative and professional manner as part of a multidisciplinary team. Bioinformatics experience would be an advantage.
Award: The PhD student will join a multi-disciplinary group under the primary supervision of Assoc Prof. Margaret Mc Gee at UCD SBBS and co-supervision of Dr. Despina Bazou (SBBS). Students will be enrolled onto a structured PhD programme in SBBS which includes some taught elements and transferrable skills training providing an excellent foundation for a research career Research Programmes at UCD
The student is required to demonstrate in appropriate laboratory practicals as part of their funded scholarship and will be remunerated at standard UCD demonstrating rates. (For more information: https://www.ucd.ie/sbbs/study/researchprogrammes/) The student will be located in UCD Conway Institute and will have access to core technologies in genomics, imaging microscopy and flow cytometry.
Scholarship stipend: €22,000 (tax-free) per annum plus full EU fees.
Project Duration: 4 years
Deadline to submit applications: 20th August 2024.
Expected project commencement date: October 2024 (or Jan 2025 latest under
exceptional circumstances)
Application procedure: To apply, please email full CV including details of two referees (3-
page max with grades) and a cover letter (2-page max) by the deadline to
(opens in a new window)margaret.mcgee@ucd.ie.
Informal queries on the project can be made to Margaret Mc Gee at the above email address.
https://www.ucd.ie/sbbs/
(opens in a new window)https://people.ucd.ie/margaret.mcgee/about