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A 3D in vitro microphysiological model of Ewing Sarcoma to study tumour biology and screen novel therapeutics.

  • Full or part time
  • Application Deadline
    Friday, May 29, 2020
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

About This PhD Project

Project Description

Despite advances in available therapies, adults and children with metastatic and/or relapsed Ewing Sarcoma have a five-year survival rate of 15-30%, highlighting the need for new treatments. One of the most promising current therapies is based on the specificity of immune effector cells to target a tumour, thus reducing systemic side effects observed with other treatments. In Ewing Sarcoma (EWS), immune cells, including tumour-infiltrating lymphocytes, macrophages, dendritic cells and natural killer (NK) cells, can either support or suppress tumour growth. Currently, a small number of immunotherapies is available to stimulate the immune system—either directly or by downregulating immune checkpoints such as programmed cell death 1 (PD1) or cytotoxic T- lymphocyte antigen 4 (CTLA-4).

However, it remains to be determined whether those promising results would hold up when eventually applied to patients with Ewing Sarcoma. However, representation of the tumour complexity and patient diversity are challenging in the identification of new agents accurately. 3D scaffold-based in vitro cell cultures are advantageous in cancer research bridging the gap between conventional 2D culture and in vivo tumours, thus increasing the likelihood of FDA approval for anti-cancer drugs. Further investigations of these communications could empower novel therapies for EWS. We aim to reconstruct the Ewing sarcoma (EWS) immune microenvironment by developing a 3D in vitro multicellular microphysiological model using collagen-based scaffolds and targeting tumour-immune cell interactions.

The proposed model will consist of two components. The first component is a collagen-based scaffold composed of glycosaminoglycan (Coll-GAG) or nanohydroxyapatite (Coll-nHA) to recapitulate the bone microenvironment in 3D. The second component is a well-characterised panel of recently established EWS cell lines. Our new 3D model will act as an adaptable system for different cellular and molecular components of the bone tumour immune microenvironment. We hypothesise that this controllable tissue-engineered 3D platform will provide new knowledge about Ewing sarcoma and will facilitate drug discovery.

The proposed project is spread between four rapidly growing biomedical areas: tumour microenvironment, immunology, tissue-engineering and drug development. A wide variety of experimental techniques across a range of disciplines will be employed in the proposed PhD project which will equip the PhD student with excellent training and skills and graduate a multidisciplinary scientist capable of combining these techniques which might be used in industry or academia.

Key references: 1. Nolan JC, Frawley T, Tighe J, Soh H, Curtin C, Piskareva O. Preclinical models for neuroblastoma: Advances and challenges. Cancer Lett. 2020 Apr 1;474:53-62. doi: 10.1016/j.canlet.2020.01.015. PMID: 31962141 2. Curtin C, Nolan JC, Conlon R, Deneweth L, Gallagher C, Tan YJ, Cavanagh BL, Asraf AZ, Harvey H, Miller-Delaney S, Shohet J, Bray I, O'Brien FJ, Stallings RL, Piskareva O. A physiologically relevant 3D collagen-based scaffold-neuroblastoma cell system exhibits chemosensitivity similar to orthotopic xenograft models. Acta Biomater. 2018 Apr 1;70:84-97. doi: 10.1016/j.actbio.2018.02.004. PubMed PMID: 29447961.

Background


This Scholarship is a new prestigious award aiming to develop future biology leaders in academia and industry. This will particularly suit ambitious doctoral candidates interested in pursuing research in medicinal biology while gaining valuable training and experience in the delivery of undergraduate teaching in Foundation Year Biology.

Programme Details


Research will be carried out in the research facility in RCSI St. Stephen’s Green. The 4-year PhD Scholarships will consist of an €18,000 annual stipend (tax free), PhD student fees and a research consumables budget.


Programme Structure


The PhD (Doctor of Philosophy) degree by dissertation is the highest postgraduate award at level 10 on the National Framework of Qualifications and represents a substantial body of research work performed over 4 calendar years. The 4year full-time Biology PhD Programme includes training in the form of taught modules/workshops.

RCSI is committed to supporting an effective supervisory system for students to ensure that the successful applicants optimise their research and career potential through the programme. Clear oversight and supervision of all PhD projects will be provided by both a Principal and Subsidiary Supervisor (co-Supervisor), and all projects are reviewed annually.

In addition, the student will teach undergraduate laboratory practicals and tutorials as required under the direction of the Head of Department or nominee (to a maximum of 6 hours per week during term time).

Requirements In order to be admitted to PhD Programme, candidates must have been awarded a 2.1 grade, or above, in a relevant accredited undergraduate degree (Honours Bachelor degree or recognised equivalent NFQ level 8 degree from an accredited Higher Education Institution). If such a degree was not obtained through the medium of English language, applicants must show certified evidence of proficiency in the English language at an IETLS level of 6.5 or above.

Application Process


The application process includes ranking the projects (listed below) by the candidate. Projects will be assigned to successful candidates based on supervisor agreement and availability.

Shortlisting of applicants will be undertaken by the panel of assessors. All shortlisted candidates will be interviewed and their referees contacted directly by RCSI. An indicative timescale is given below.

Applications Open: 10 March 2020
Applications Close: 29 May 2020 (17:00 GMT)
Shortlisting: 18 June 2020
Interviews: End-June 2020 (Skype may be used)
Position begins: October 2020

How do I apply?


Download and fill in the Application Form found here:
- Only applications submitted through this form will be accepted: https://forms.office.com/Pages/ResponsePage.aspx?id=50FwYBKocEa9MDD52yEPBhzgnmH8dBtPo-wzaX6dfsdUNEwzMVhQVTZZUUswR1RISU1GMTAyNjkxRy4u
- Shortlisted candidates will be invited for interview.
- Only their referees will also be contacted at this stage for a reference.
- Interviews will be held at RCSI Dublin (123 St Stephen’s Green). Skype may be used if necessary.
- The Head of the School will offer the successful candidate a scholarship. -
- Only at this stage does the candidate go through the formal registration process using the ‘Apply Online’ system at RCSI.

Applications must include:
(i) a completed application form
(ii) English language requirements – see https://www.rcsi.com/dublin/postgraduate/policies-and-guidelines/english-language-requirements.

All documents must be:
- in PDF format
- in English
- accessible, clear and legible
- easily identifiable

Please label all files in the following format: Biology_PhD_2016_CV_JoeyBloggs.pdf. Replace "_CV" with "_letter", "_form" or "_transcript" as appropriate.

Deadline All applications must be made online by Friday 29th May 2020 (17:00 GMT).

It is the candidate’s responsibility to ensure that all documents are submitted on time. Late and/or incomplete applications will not normally be assessed. Only applications submitted through the School of Postgraduate Studies Recruitment portal will be considered. Do not send CVs directly to projects leads.

Contact details For enquiries please contact Dr Olga Piskareva at . For technical queries regarding application submission please contact Dr Anthony Chubb at .

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