Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

3 fully funded PhDs: Clement Archer School of Pharmacy PhD Scholarship

The Royal College of Surgeons in Ireland (RCSI) is a private, self-financing, not-for-profit medical and surgical college headquartered in Dublin (Ireland) with global reach through its overseas medical universities and health care centres in the Middle East, the Far East and Africa. Since its foundation in 1784, it has played a leadership role in Irish surgical and medical education. Currently, it operates the largest Medical School in Ireland and provides undergraduate education in Physiotherapy, Pharmacy, and Nursing. In addition to Surgery, it also provides postgraduate training and education in Radiology, Dentistry, Nursing & Midwifery, Sports and Exercise Medicine, Healthcare Management and Leadership, and has an Institute of Research. DESCRIPTION: Expressions of Interest are invited for three Clement Archer Scholar positions in the RCSI School of Pharmacy. As part of this role, the successful applicants will each be registered for a funded PhD, with the School covering the tuition fees and providing an annual stipend of €18,000. An international travel grant of €1,500 is also included to support an international excursion undertaken throughout the research study. Scholar activities will include a combination of laboratory/practical demonstrations, tutorials, lecturing, supervision of undergraduate research students, outreach activities, assessment and correcting. Some or all of these activities will comprise a maximum of 1.5 days per week during each academic term. Scholars will have the choice of selecting one of the six research studies described below which upon successful completion will lead to the award of an NUI/RCSI Doctorate in Philosophy (PhD).

Project Options

 

1. Medicines Optimisation for Patients Living with Cancer and Receiving Palliative Care. 

Medicines optimisation for cancer patients receiving palliative care is a major challenge to improving quality of life and an under-researched area. At diagnosis, cancer patients often have existing comorbidities necessitating use of multiple medications (polypharmacy). Optimising medication regimens requires clinicians to consider whether each medication is appropriate in relation to patients’ treatment goals and life expectancy. 

Targeted action is needed to improve medicines management in patients living with cancer, particularly in end-of-life settings. There is currently limited research on how to do this in clinical practice. This mixed-methods project will seek to investigate prescribing practices for patients living with cancer and receiving palliative care, and develop a strategy for medicines optimisation in this cohort of patients. The successful candidate will gain skills in both quantitative and qualitative research methods, which are widely used in health services research.

The PhD project will run in parallel with a research project that is being funded by the Irish Cancer Society and the All Ireland Institute of Hospice and Palliative Care.

Project 1 Main Supervisor: Dr. Cathal Cadogan

Co-Supervisor: Prof. Kathleen Bennett (RCSI Division of Population and Health Sciences)

Further project enquiries to: Dr. Cathal Cadogan (email: cathalcadogan@rcsi.ie)

 

2. Evaluation of eHealth Technologies Relating to Prescribing, Dispensing, Administration and Monitoring of Medication. 

We are in a transformative period in Irish healthcare currently as we attempt to move from paper-based medical records and prescribing to electronic systems. The creation of the HSE subsidiary, eHealth Ireland, has accelerated efforts to meet this goal. A number of initiatives are now under way under the eHealth Ireland umbrella with the aim to evaluate and assess potential technological solutions and inform activities going forward.

One of the larger scale, and more successful initiatives currently in operation is the introduction of the Maternal & New-born Clinical Management System (MN-CMS). This is a fully Electronic Health Record (EHR) which has recently been introduced in several hospitals around the country and is due to be introduced to fifteen others on a phased basis from 2019. Before this can progress to a large scale roll-out, the system must be evaluated and the benefits of it, to staff and patients alike clearly quantified with any short fallings identified and addressed. 

The aims of this project therefore are (i) to evaluate the current EHR in the context of a number of important outcomes, and (ii) based on these findings, develop suitable interventions to address the deficiencies identified and hence ensure that future iterations of the EHR are fit for purpose. This body of work will be highly beneficial to eHealth Ireland as they review these early versions of the EHR and incorporate generalisable research findings to improve future EHR implementations. 

The project will follow a mixed methods approach and will include both qualitative and quantitative research. The successful candidate will gain skills in a wide variety of research methods and ultimately contribute to shaping the eHealth infrastructure in Ireland.

Project 2 Main Supervisor: Dr. Shane Cullinan

Co-Supervisor: Prof. Brian Cleary (RCSI School of Pharmacy [Honorary] and Rotunda Hospital)

Further project enquiries to: Dr. Shane Cullinan (email: shanecullinan@rcsi.ie)

 

3. A Novel Platform to Improve Oral Delivery of Therapeutic Peptides. 

Biomedical research has played a significant role in identification and elucidation of new drug targets as well as discovery of drug candidates with improved efficacy, safety and tolerability. In modern drug discovery, chemical entities that exhibit these desirable characteristics are generally larger and of greater molecular complexity. In the last 75 years, drugs have become progressively larger and more complex, which has led to greater demand for innovative drug delivery technologies.

Peptides are potent modulators of cell signalling with a history of safe use in man. The therapeutic potential of this molecular class is however restricted pre-systemic degradation and poor intestinal permeability resulting from the inability of hydrophilic macromolecules to permeate intestinal epithelial cells. As a result, the majority of marketed peptides must be administered as inconvenient injections. A delivery platform that allows peptides to be consistently and efficiently delivered via the oral route would transform early discovery pipelines and could permit reformulation of several injectable peptides.

This project will study the physicochemical parameters that govern peptide permeation across the intestinal epithelium and develop a delivery platform that improves passive transcellular flux and bioavailability. The project will run in collaboration with the David Brayden’s delivery group in University College Dublin. Studies will employ in vitro, ex vivo and in situ intestinal permeability models, and training will be provided for mammalian cell and tissue based delivery models, relevant analytical techniques (HPLC, ELISA, spectrofluorimetry, DLS) and bioassays (cell culture, histological assessment). 

Applicants are expected to be highly motivated and express an interest in pharmaceutics and drug delivery sciences. 

Project 3 Main Supervisor: Dr. Sam Maher

Co-Supervisor: Prof. David J. Brayden (UCD School of Veterinary Medicine and Conway Institute)

Further project enquiries to: Dr. Sam Maher (email: sammaher@rcsi.ie) 

 

4. Determination of the Stability of Drug:Food Combinations for Paediatric Administration. 

The administration of oral dosage forms to children presents significant and specific challenges which do not typically arise in other population groups. Due to a lack of age-appropriate formulations, depending on speciality, up to 90% of medicines used in children are used off-label i.e. a medicine designed for adult administration is given by necessity to a child. As a result of lack of age appropriate formulations dosage forms are often manipulated to facilitate their administration to paediatric patients. Some of the most common manipulations include tablet crushing/capsule opening and mixing with various foods to increase ease of swallowing and acceptability for younger patients. However, disruption of an intact oral dosage form may compromise the physicochemical stability of the active pharmaceutical ingredient (API), altering its bioavailability and efficacy. A recent EMA guideline requires that “the effect of mixing the product with common food or drinks as specified by the applicant should be discussed for every oral paediatric medicinal product”. 

The off label manipulation and co-administration of drugs with foodstuffs currently occurs despite a lack of clinical or industrial guidance on drug stability in different foods. This study aims to address these gaps by assessing the physicochemical stability of APIs when mixed with common paediatric foods. Outputs from this study will contribute to an industry standard suite of food and liquids and will allow for a correlation to be drawn between stability of drug and the properties of various paediatric foods.

The proposed project represents collaboration between academic and industrial members of the European Paediatric Formulation Initiative (EuPFI). Academic support will come from RCSI and the University of Hertfordshire and Industrial mentorship and training from Glaxo SmithKline, UK and Merck, USA. 

Project 4 Main Supervisor: Dr. Fiona O’Brien

Co-Supervisor: Dr. Fang Liu (University of Hertfordshire), Dr. Alison Keating (RCSI School of Pharmacy)

Further project enquiries to: Dr. Fiona O’Brien (email: fionaobrien@rcsi.ie) 

 

5. The Development of a Novel Inhalable Therapeutic for the Treatment of Idiopathic Pulmonary Fibrosis.

Today, idiopathic pulmonary fibrosis (IPF) is an incurable disease that causes rapid deterioration of respiratory function and death within three years of diagnosis. Devastatingly, despite the recent approval of two drugs for IPF, neither drug has definitively shown a reduction in patient mortality, highlighting a critical need for the translation of new therapeutics into the clinic. Although the precise pathophysiological mechanisms of IPF are not fully understood, chronic repetitive injury to alveolar epithelial cells, dysregulated epithelial-fibroblast intercellular communication, and aberrant immune responses are all implicated in disease progression. Together, these events stimulate the generation of extracellular matrix (ECM)-producing myofibroblasts that remodel lung tissue with excessive, fibrotic ECM. Accordingly, the development of novel medicines that target such mechanisms has the potential to offer new therapeutic pathways for IPF. Moreover, these medicines should also ideally be delivered via the respiratory tract for maximal local therapeutic activity at the site of tissue dysfunction and damage, as well as to reduce systemic side effects that severely limit the use of established oral therapies.

Recent work by our group has identified an off-patent drug with potential to be repurposed as a novel anti-fibrotic. A preliminary in-house inhalable formulation was examined and found to reduce the expression of pro-fibrotic molecules involved in IPF pathogenesis. However, the precise inhalable formulation for this drug and its activity against the fibroblastic and immunological components of IPF have yet to be determined.

Therefore, the major objective of this PhD project is to develop an inhalable formulation with future potential as a therapy for the treatment of IPF. Our central hypothesis is that the off-patent drug can be re-purposed into one or more pulmonary drug formulations that can be validated through analysis of efficacy in in vitro cell models and an in vivo model of IPF. To achieve this, the specific project aims are:

 

1. The manufacture and characterisation of dry powder and nebulised drug formulations as two inhalable anti-fibrotic therapeutics for IPF.

2. The in vitro assessment of inhaled formulations in respiratory cell models of alveolar epithelial cells and lung fibroblasts.

3. The ex vivo assessment of inhaled formulations in alveolar macrophages isolated from patients with IPF.

4. The in vivo assessment of inhaled formulations in an animal model of pulmonary fibrosis.

 

The scholar will be primarily based in the School of Pharmacy and Tissue Engineering Research Group at RCSI and will work closely with other members of a multidisciplinary project team including pharmacists, clinicians, and engineers. Additionally, they will have to the opportunity to perform research in a clinical laboratory setting with patient-specific, ethically-obtained samples at Beaumont Hospital. Overall, this project will provide the scholar the opportunity to develop a new medicinal product with real clinical and commercial potential that can answer a currently unmet clinical need.

 

Project 5 Main Supervisor: Dr. Cian O’Leary

Co-Supervisor: Prof. Sally Ann Cryan (RCSI School of Pharmacy), Dr. Killian Hurley (RCSI Beaumont Hospital)

Further project enquiries to: Dr. Cian O’Leary (email: cianoleary@rcsi.ie)

 

6. Synthesis and Evaluation of a Multi-Functional Compound for Resistant Depression: A Roadmap to a New Class of Antidepressant Agent.

Depression affects 350 million people globally and current treatment options are insufficient given their limited therapeutic efficacy in many patients. Indeed, currently available antidepressants show an efficacy rate of just 70% leaving many patients with an unmet clinical need. These antidepressant resistant patients represent a subset of the depressed population for whom current medications developed using the monoamine hypothesis of depression prove ineffective and for whom new therapeutic avenues must be pursued.

While the aetiology of depression is incompletely understood, a number of risk factors have been identified, including genetic, epigenetic, environmental and endocrine. One such endocrine disorder is type II diabetes. Type II diabetes has been shown to co-occur with depression with epidemiological evidence pointing to a bi-directional relationship. A diagnosis of type II diabetes increases both the risk of depression and the severity of the disease course while also predisposing the patient to treatment resistant depression.

As a multi-factorial disease, depression is an ideal candidate for multi-functional compound drug therapy. Multi-functional drug compounds confer a number of distinct clinical advantages, including, of particular importance to the manifestation of depression, synergistic therapeutic responses. The development of a new hybrid molecule that successfully addresses the complexity of depression pathophysiology should greatly assist in alleviating symptoms in patients with a diagnosis of depression, including those in whom depressive symptoms do not remit in spite of appropriate drug therapy with standard anti-depressant medication.

Therefore, the overarching aim of this project is to synthesise and pharmacologically using in vivo electrophysiological and behavioural models evaluate a completely new class of antidepressant with dual functionality, having two distinct pharmacophores, a moiety which behaves akin to a standard antidepressant, and a moiety which alters glucose handling. This new therapeutic class with synergistic biological activity we predict will offer a new treatment path for depressed patients in whom current treatment options are sub-optimal. This strategy has been validated in several potential therapeutic applications, with diverse molecular frameworks, including in the laboratory of the supervisors.

The successful candidate will join the multi-disciplinary Neuropharmacology Research Group whose research focus is on enhancing our scientific understanding of treatment resistant depression, through which new therapeutic options are developed which can make a meaningful difference to patients.

Project 6 Main Supervisor: Dr. Ben Ryan

Co-Supervisor: Dr. James Barlow (RCSI Pharmaceutical & Medicinal Chemistry Department)

Further project enquiries to: Dr. Ben Ryan (email: benedictryan@rcsi.ie)

 

Additional Information

Applicants are asked indicate their specific PhD project of interest in their cover letter. If applicants have further queries on the listed projects in this competition they are welcome to directly email the main supervisor.

Specifically the duties of this post will include (but are not limited to) the following: 


Scholar Roles and Responsibilities

  • Coordinating and delivering teaching activities (lectures and tutorials) and lab practicals: commitments will include coordination and supervision of practicals as agreed with the relevant module leader, in conjunction with the Head of School.
  • Liaising with technicians with respect of setup/materials required for practicals.
  • Preparation and correction of student practical manuals and lab books/demonstrator lab books. 
  • Responding to student queries relating to practicals. 
  • Contributing to the assessment of other modules as agreed with your Supervisor, in conjunction with the Head of School.
  • Delivery of lectures related to the Scholar’s area of expertise (in Years 3 and 4 of the PhD).
  • Participation in School outreach activities as agreed with your Supervisor, in conjunction with the Head of School.

PhD Activities

  • Researching, planning and conducting experiments required to achieve the aims and objectives of the PhD project.
  • Taking direction from Principal Investigator but also operating independently once direction has been set.
  • Carrying out own research work to deadlines.
  • Keeping up to date with relevant publications in the field.
  • Preparing annual reports and meeting administrative requirements of any funding agencies and the RCSI School of Postgraduate Studies.
  • Undertaking Scholar activities as agreed in conjunction with your Supervisor and the Head of School.
  • Recording all methods and results to Departmental and College standards.

General Duties:

  • Working in a co-operative fashion and as an effective team member.
  • Complying with statutory legislation and School rules and requirements in furtherance of your own general welfare and safety, along with that of your colleagues. 
  • Undergoing programmes of training and development as may be required from time to time.
  • Representing the best interests of the School/College at all times.

   Personal Specification

  • A primary degree in pharmacy is preferable but not a necessity.
  • Applications are invited from enthusiastic and highly motivated individuals with a keen interest in a relevant area of Pharmacy research. 
  • English language requirements for candidates who do not speak English as a first language: an overall IELTS score of 6.5.  
  • Candidates should display: 
    • A good knowledge base, with evidence of interest in their research area of choice 
    • A capacity for independent thinking 
    • A professional work ethic 
    • The ability to organise themselves 
    • A willingness to learn 
    • Innovation and creativity
    • Excellent interpersonal, communication and presentation skills 
    • A capacity to work collaboratively as part of a team as well as independently, in a non-structured environment
    • Attention to detail, thoroughness in work practices and an ability to work to deadlines

Application process

Applications for this post must be made via the RCSI Careers website at www.rcsi.ie/careers  

Closing date for receipt of applications is 5pm on  Monday, April 30th 2018.

Please include a CV and a detailed covering letter outlining your suitability for this role and specifying your project of interest.  

 

Queries:

  • For any queries relating to the application process, please contact Judy Walsh in the RCSI HR department on +353-1-402-2440 or by email at recruitment@rcsi.ie  
  • Ms. Walsh can arrange for relevant queries on the academic aspects of the role to be addressed by Prof. Paul Gallagher (Head of School).

 

Note: this Job Description may be subject to change to reflect the evolving requirements of the Department and RCSI in developing healthcare leaders who make a difference worldwide.

RCSI is an equal opportunities employer.


Mentors Prof. Paul Gallagher