New therapeutic agents against triple negative breast cancer – targeting an unmet clinical need with the second generation Pol I inhibitor, PMR-116.
Applications are now CLOSED
Overview
This project aims to develop novel therapies for triple-negative breast cancer by combining novel and old drugs to enhance treatment efficacy and reduce side effects.
Breast Cancer (BCa) is a heterogeneous disease with various molecular subtypes and associated outcomes, currently the most common malignancy worldwide. Triple-negative breast cancer (TNBC) accounts for 15-20% of all BCa, and has the highest rates of distant relapse (~50%) and mortality. Treatment of TNBC is challenged by its lack of specific targets. The newest therapeutic advances, such as PARP inhibitors, antibody-drug conjugates, and immune checkpoint inhibitors, offer no benefit to the majority of TNBC patients. This underscores the urgency for novel precision therapies to improve outcomes for TNBC patients.
One such opportunity involves 2nd-generation Pol I transcription inhibitor (PMR-116) and the first-in-class pan-inhibitor of KDM4 histone demethylase (TACH101). These compounds are currently in Phase 1 clinical trials for advanced solid tumours, including TNBC and other metastatic BCa (ACTRN12620001146987 and NCT05076552, respectively). Preliminary data from the KP lab show synergy between epirubicin and PMR-116. Furthermore, knockdown of histone demethylase KDM4 appears to sensitise TNBC cells to Pol I inhibition, revealing an opportunity to enhance the efficacy of Pol I inhibition, by incorporating the KDM4 inhibitor TACH101 into the treatment regime. Combined, this can enable the development of effective treatments which could reduce anthracycline doses, reducing its adverse effects.
The KP lab’s exclusive access to PMR-116, commercial availability of TACH101 and access to established preclinical, orthotopic, immune competent TNBC models (CB lab), and TNBC expertise in biomarker development (PM)will enable this multidisciplinary team to:
(1) Determine the efficacy of the PMR-116 and epirubicin combination in treating TNBC (CB lab)
(2) Explore and validate the effect of KDM4 inhibition by TACH101 on PMR-116 efficacy (KP lab)
(3) Identify predictive biomarkers for treatment response and prognosis (PM lab).
This research projects investigates the clinical properties of new anticancer drugs in combination with well-established ones or with other novel drugs have the potential to discover synergistic effects that enhance treatment efficacy, reduce side effects, and overcome drug resistance. This aligns with Queen's ambition to "shape a better world through life-changing education and research" and its commitment to "address real-world needs" through high-impact research”. This interdisciplinary collaboration, in the area of One Health, with Hannan group, ANU and Pimera Inc, USA will enhance the impact of this project’s outputs and supports the University's goal of driving social and economic change with global resonance, reinforcing Queen's position as a leader in innovative healthcare research and clinical excellence.
Funding Information
One Health and QUB
Only candidates who do not qualify for Home fee status at the University may apply. Information on fee status is available from the University website: View Website
To be considered for the project you must apply through the Direct Applications Portal: View Website
Project Summary
Dr Konstantin Panov
Full-time: 3 Years
Biological Sciences overview
The School of Biological Sciences provides PhD and MPhil (research degree) programmes in subjects ranging from basic biochemistry, molecular genetics and cancer research, to agricultural science, marine ecology and the economic evaluation of ecosystem services and food retailing. If you have a topic or research question in mind, please use the Find a Supervisor link (see Apply tab) to identify the most appropriate member of staff to support your idea. If not, don't worry, we regularly advertise funded projects and there is no harm in browsing our academic staff profiles for inspiration and then contacting whoever seems best: we are very open to applications from suitably qualified people interested in scientific research. In every case, a PhD or MPhil course provides the means of being part of a cutting edge scientific research team and contributing to genuine new discoveries or the development of new methods for practical use. If you cannot study full time, we offer pro-rata part time research degree programmes as well.
There are three broad themes to research at the School:
- Agri-Food Systems and Human Nutrition
- Understanding Health and Disease
- Sustaining Ecosystems and Biodiversity
Agri-Food Systems and Human Nutrition:
This theme focuses on how Agri-Food systems can be better positioned to provide safe, authentic and healthy diets with high-quality plant, livestock, and aquaculture products, whilst supporting human and animal health in a way that is sustainable and resilient to climactic changes.
Underpinning these goals, the disciplinary expertise of the theme integrates basic and applied research from animal health and welfare, nutrition, performance, and environmental and social impact (e.g. greenhouse gas emissions from livestock) to chemical contaminant and natural toxin detection, food microbiology, food fraud detection, and food systems traceability and transparency, integrated into a holistic total systems approach.
Supporting by underpinning expertise in cutting-edge molecular, genomic, transcriptomic, proteomic, and metabolomic technologies, artificial intelligence and simulation modelling, the goal of the theme is to support the transformation of global Agri-Food systems. This is with the purpose of maximising the benefits both to animal and human nutrition and health, while simultaneously reducing environmental impact, protecting ecological resources, supporting livelihoods and access to affordable safe foods, and upholding social, cultural, and ethical values. A system based on the principles of measurable integrity and impact.
Understanding Health and Disease:
The Understanding Health and Disease research theme covers humans, plants, and animals with research strengths in prevention, diagnostics, surveillance, epidemiology, and treatments. We study how health can be improved through food and nutrition and how diseases can be tackled by understanding their fundamental molecular mechanisms, including those underpinning the biology of pathogens and parasites. Our researchers work in human cancer and genetic diseases, in infections caused by bacteria, fungi, viruses, and parasites, and in how global health and disease will be affected by global warming and climate change.
We recognize that the only way to tackle the problems we face as a society is to take an interdisciplinary approach to our research. This means we have expertise in broad areas including molecular biology, biochemistry, bioinformatics, genomics, transcriptomics, modelling, bioanalytical chemistry, proteomics, metabolomics, microbiology, parasitology, and plant biology. We work internationally with researchers and partners in universities, charities, non-governmental organisations, industry, and government agencies to tackle local and global challenges.
Sustaining Ecosystems and Biodiversity:
This theme covers research in biodiversity and ecosystem services for environments ranging from tropical forests to deep oceans, using field techniques and skills such as wildlife tracking, taxonomy, geostatistics, molecular and genetic ecology, environmental microbiology, microbial ecology, food web analysis, microcosm and mesocosm experiments, and mathematical/computational methods. Within this theme we also study the behaviour and temperament of wild, agricultural or domestic animals and their implications for welfare and ability to respond to environmental change.
Potential research projects include phylogenetic analysis of rare and newly discovered species, examination of ecological interactions in tropical systems, agricultural soils, or marine communities, using state-of-the-art genetic analysis, surveys using drones or satellite tagging, or experiments in tanks and field plots, including careful and ethical examinations of animal behaviour. Projects range from theoretical analysis of stability in ecosystems, through discovery of new species and mechanisms of interaction, or responses to climate change, to the assessment of agri-environment schemes, development of new methods for commercial fisheries management and economic evaluations of conservation measures. Projects very often have an international dimension and include collaboration with other researchers worldwide.
Biological Sciences Highlights
Industry Links
- The School has a wide range of strong, international links with governments, academia and industry, into which postgraduate research students are integrated.
World Class Facilities
- Research students will have access to laboratory space as required (in our state-of-the-art research laboratories) and where relevant, also a range of field study sites and equipment (e.g. remote sensing drone equipment). They also have access to local and campus-wide high performance computing facilities and the full strength of our world-class library. Many students also benefit from the strong collaboration network maintained by our academic staff, which could result in working in the laboratories of partner organisations in industry and government as well as in the University, under specific arrangements.
- Students studying in the Food Safety and Nutrition programme will gain excellent practical experience of advanced technology and bioanalytical techniques for food safety analysis and monitoring, including:
1. GC, HPLC and UPLC separation platforms;
2. ICP, IR, qToF and QqQ mass spectrometers;
3. Microbiological research facilities;
4. Antibody production and biomolecule binder development;
5. Cell culture suite and bioanalytical assay detection systems;
6. NMR, NIR and Raman spectrometers;
7. Proteomic and metabolomic profiling tools RT-PCR;
8. Transcriptomic profiling;
9. Next-generation sequencing;
10. Multiplex biosensor platforms and LFD development.
Internationally Renowned Experts
- Research at Institute for Global Food Security and the School of Biological Sciences was rated 1st in the UK in the latest Research Exercise Framework (REF) – an independent assessment of research quality, impact and environment at UK universities.
IGFS/Biological Sciences topped the national league table for Agriculture, Veterinary and Food Science, with 94% of research in those areas deemed “world-leading” or “internationally excellent”.
Additionally, the research environment at IGFS/SBS scored a phenomenal 100%.
Key Facts
- Most of the critical problems facing humanity - disease, climate change and food security - require biological understanding to solve them.
Course content
Research Information
PhD Supervisors
Information on the research interests and activities of academics in Biological Sciences can be accessed via the School website and the Find a Supervisor facility (see Apply tab).
Career Prospects
Introduction
Queen's postgraduates reap exceptional benefits. Unique initiatives, such as Degree Plus and Researcher Plus bolster our commitment to employability, while innovative leadership and executive programmes alongside sterling integration with business experts helps our students gain key leadership positions both nationally and internationally.
Career prospects in the biological sciences are exceptionally good. To some extent it depends on the specific topic, of course, but laboratory-based and especially quantitative skills and the proven innovation of a PhD or MPhil are highly sought after. Degrees are very much in demand, both in commercial science and public sector research and development (e.g. drug discovery and development, crop and animal improvements and welfare, sustainable agriculture and resource use, human nutrition and health, animal health, ecological management, food safety and technology, scientific communications, regulation, and many more fields).
Employment after the Course
Graduates have gone on to be professional research scientists, consultants, or hold technical and junior executive positions in commerce and government.
People teaching you
Dr Gareth Arnott
Postgraduate Research Director
School of Biological Sciences
For a PhD you will have a principal and second supervisor who advise your independent studies and will be supported by a wider team from the academic staff - who they are, of course, depends on your project. For further details on any aspect of postgraduate research degrees within the School of Biological Sciences, contact: biosciences-pg@qub.ac.uk.
Research degrees are overseen by the School of Biological Sciences Director of Postgraduate Research, who currently is Dr Gareth Arnott.
Learning Outcomes
A postgraduate research degree involves the undertaking of independent research under the guidance of a professional academic supervisory team, typically using the laboratory facilities on offer in one or more of the teams' labs. The student will be expected to develop their own ideas and learn the methods needed to test them empirically and theoretically. This usually involves learning and practising both laboratory (and or field) skills as well as developing a strong theoretical background in the relevant subject.As well as practical work, all the activities of independent academic scholarship, such as literature searching and critical appraisal, written and verbal communications and academic networking will be developed during a research degree. Independence and innovation will be strongly encouraged, but the student will be supported by regular supervisory guidance and a wide range of courses will also be on offer, both in subject specific skills and generic skills, especially supported by the Graduate School (https://www.qub.ac.uk/graduate-school/).
Students are encouraged to interact with one another and with members of academic staff and postdoctoral scientists to build confidence and informal learning, through a range of ‘research culture’ activities, including peer groups where students get together to discuss topical research papers, or methods, or just chat about their interests.
Course structure
Research degrees vary in length, but typically for a PhD they are three or four years long (full-time) and double that for part-time studies. They follow an annual cycle of progress with formal panel-based appraisals of the progress, the outcome of which is typically practical and academic advice about how to overcome problems encountered and how to move to the next stage. During each year, students are expected to supplement their studies with some tailored courses, ranging from highly specific (e.g. learning to use a piece of apparatus or technique) to generic (e.g. developing oral presentation or leadership skills). Every stage is supported by the supervisory team, augmented by an independent panel of progress monitors as well as the full support of the Graduate School.Assessment
Assessment processes for the Research Degree differ from taught degrees. Students will be expected to present drafts of their work at regular intervals to their supervisor who will provide written and oral feedback; a formal assessment process takes place annually.
This Annual Progress Review requires students to present their work in writing and orally to a panel of academics from within the School. Successful completion of this process will allow students to register for the next academic year.
The final assessment of the doctoral degree is both oral and written. Students will submit their thesis to an internal and external examining team who will review the written thesis before inviting the student to orally defend their work at a Viva Voce.
Feedback
Supervisors will offer feedback on draft work at regular intervals throughout the period of registration on the degree.
Facilities
Full-time research students will have access to a desk in a shared office space.
Entrance requirements
Graduate
The minimum academic requirement for admission to a research degree programme is normally an Upper Second Class Honours degree in a relevant subject from a UK or ROI HE provider, or an equivalent qualification acceptable to the University. Further information can be obtained by contacting the School.
International Students
For information on international qualification equivalents, please check the specific information for your country.
English Language Requirements
Evidence of an IELTS* score of 6.5, with not less than 5.5 in any component, or an equivalent qualification acceptable to the University is required (*taken within the last 2 years).
International students wishing to apply to Queen's University Belfast (and for whom English is not their first language), must be able to demonstrate their proficiency in English in order to benefit fully from their course of study or research. Non-EEA nationals must also satisfy UK Visas and Immigration (UKVI) immigration requirements for English language for visa purposes.
For more information on English Language requirements for EEA and non-EEA nationals see: www.qub.ac.uk/EnglishLanguageReqs.
If you need to improve your English language skills before you enter this degree programme, INTO Queen's University Belfast offers a range of English language courses. These intensive and flexible courses are designed to improve your English ability for admission to this degree.
Tuition Fees
Northern Ireland (NI) 1 | TBC |
Republic of Ireland (ROI) 2 | TBC |
England, Scotland or Wales (GB) 1 | TBC |
EU Other 3 | £25,600 |
International | £25,600 |
1 EU citizens in the EU Settlement Scheme, with settled or pre-settled status, are expected to be charged the NI or GB tuition fee based on where they are ordinarily resident, however this is provisional and subject to the publication of the Northern Ireland Assembly Student Fees Regulations. Students who are ROI nationals resident in GB are expected to be charged the GB fee, however this is provisional and subject to the publication of the Northern Ireland Assembly student fees Regulations.
2 It is expected that EU students who are ROI nationals resident in ROI will be eligible for NI tuition fees. The tuition fee set out above is provisional and subject to the publication of the Northern Ireland Assembly student fees Regulations.
3 EU Other students (excludes Republic of Ireland nationals living in GB, NI or ROI) are charged tuition fees in line with international fees.
All tuition fees quoted are for the academic year 2021-22, and relate to a single year of study unless stated otherwise. Tuition fees will be subject to an annual inflationary increase, unless explicitly stated otherwise.
More information on postgraduate tuition fees.
Biological Sciences costs
Students may incur additional costs for small items of clothing and/or equipment necessary for lab or field work
Additional course costs
All Students
Depending on the programme of study, there may also be other extra costs which are not covered by tuition fees, which students will need to consider when planning their studies . Students can borrow books and access online learning resources from any Queen's library. If students wish to purchase recommended texts, rather than borrow them from the University Library, prices per text can range from £30 to £100. Students should also budget between £30 to £100 per year for photocopying, memory sticks and printing charges. Students may wish to consider purchasing an electronic device; costs will vary depending on the specification of the model chosen. There are also additional charges for graduation ceremonies, and library fines. In undertaking a research project students may incur costs associated with transport and/or materials, and there will also be additional costs for printing and binding the thesis. There may also be individually tailored research project expenses and students should consult directly with the School for further information.
Bench fees
Some research programmes incur an additional annual charge on top of the tuition fees, often referred to as a bench fee. Bench fees are charged when a programme (or a specific project) incurs extra costs such as those involved with specialist laboratory or field work. If you are required to pay bench fees they will be detailed on your offer letter. If you have any questions about Bench Fees these should be raised with your School at the application stage. Please note that, if you are being funded you will need to ensure your sponsor is aware of and has agreed to fund these additional costs before accepting your place.
How do I fund my study?
1.PhD OpportunitiesFind PhD opportunities and funded studentships by subject area.
2.Funded Doctoral Training ProgrammesWe offer numerous opportunities for funded doctoral study in a world-class research environment. Our centres and partnerships, aim to seek out and nurture outstanding postgraduate research students, and provide targeted training and skills development.
3.PhD loansThe Government offers doctoral loans of up to £26,445 for PhDs and equivalent postgraduate research programmes for English- or Welsh-resident UK and EU students.
4.International ScholarshipsInformation on Postgraduate Research scholarships for international students.
Funding and Scholarships
The Funding & Scholarship Finder helps prospective and current students find funding to help cover costs towards a whole range of study related expenses.
How to Apply
Apply using our online Postgraduate Applications Portal and follow the step-by-step instructions on how to apply.
Find a supervisor
If you're interested in a particular project, we suggest you contact the relevant academic before you apply, to introduce yourself and ask questions.
To find a potential supervisor aligned with your area of interest, or if you are unsure of who to contact, look through the staff profiles linked here.
You might be asked to provide a short outline of your proposal to help us identify potential supervisors.