Faculty of Medicine and Health
School of Medicine
Leeds Institute of Cardiovascular & Metabolic Medicine (LICAMM)
Division of Cardiovascular & Diabetes Research
Research Fellow
Fixed Term for Three Years
100% of full time basis
Project Title: Regulation of T-type calcium channels by heme oxygenase-1 derived carbon
monoxide: a novel target signalling pathway for the treatment of vascular diseases.
An exciting research position is available immediately for a fixed term of three years which has been
successfully awarded by the British Heart Foundation (BHF). This is a collaborative study between the
Faculty of Medicine & Health (FOMH) and Faculty of Biological Sciences (FBS) and will be based in the
laboratory of Professor Chris Peers, Dr John Boyle and Dr Jason L Scragg (FOMH) and will also engage
the expertise of Professor Mark Kearney (FOMH) and Dr Jon Lippiat (FBS).
The project aims to investigate the mechanisms by which CO regulates T-type Ca2+ channels and, in so
doing, regulates vascular smooth muscle cell proliferation associated with numerous cardiovascular
diseases. We aim to establish these important effects of CO at the molecular, cellular and intact, in vivo
level, in order to describe fully the signalling cascades involved in CO-regulation of this key ion channel.
The successful applicant will be responsible for the electrophysiological, pharmacological and biochemical
experiments and will contribute to the in vivo work for which training will be provided. They will also have
responsibility for appropriate data analysis and will present their work to the laboratory, in scientific
publications and at scientific meetings.
Applicants will have a PhD in physiology, pharmacology, biochemistry (or equivalent); applications will be
accepted from individuals who are nearing completion of their PhD, or who have already submitted their
thesis. In such cases any offer would be made subject to successful PhD completion within a specific
timeframe. The project is multidisciplinary and involves electrophysiological, imaging, biochemical,
molecular-biological and in vivo studies therefore experience in at least some of these methods is essential.
This post is available on a 3 year fixed term basis. This position is subject to Security Vetting.
The University of Leeds is committed to providing equal opportunities for all and offers a range of
family friendly policies (http://hr.leeds.ac.uk/homepage/4/policies). The University is a charter
member of Athena SWAN and holds the Bronze award. The School of Medicine gained the Bronze
award in 2013. We are committed to being an inclusive medical school that values all staff, and we
are happy to consider job share applications and requests for flexible working arrangements from
our employees.
University Grade 7 (£31,342 – £37,394 p.a.) depending on qualifications and experience. Please
note we can only offer a salary up to £35,256 (SP34) due to the amount awarded.
Informal enquiries regarding the post should be directed to Professor Christopher Peers,
telephone +44 (0)113 343 4821 or email c.s.peers@leeds.ac.uk.
If you have any specific enquiries about your online application please contact Sou Sit Chung, telephone
+44 (0)113 343 9177 or email licamm-hr@leeds.ac.uk.
Job Ref: MHLCM1038
Closing Date: 11 September 2015
Purpose of the Post
The project aims to investigate the mechanisms by which CO regulates T-type Ca2+ channels and,
in so doing, regulates vascular smooth muscle cell proliferation associated with numerous
cardiovascular diseases. We aim to establish these important effects of CO at the molecular,
cellular and intact, in vivo level, in order to describe fully the signalling cascades involved in COregulation of this key ion channel.
Background
Vascular smooth muscle cells (VSMCs) control vascular tone, flow and distribution of blood. They
also undergo phenotypic changes, becoming non-contractile, proliferative cells to adapt to varying
physiological and pathological situations. This is crucial in development, vasculogenesis and
vascular repair but is also crucially important in the development of cardiovascular diseases.
Improved understanding of how to control VSMC proliferation therefore has tremendous
therapeutic potential.
Systemic VSMC proliferation is a key feature of numerous diseases. Proliferation and migration
also underlie neointimal hyperplasia which causes restenosis, limiting the success of coronary
artery bypass grafting, balloon angioplasty and stent implantation. Although complex, the process
of switching from a contractile to a proliferative phenotype during disease progression consistently
features two key aspects of fundamental importance, namely (i) altered expression of key VSMC
ion channels, and (ii) increased expression of the heme degrading enzyme, heme oxygenase-1
(HO-1), which generates the signalling molecule carbon monoxide (CO). Our BHF-funded work
over several years has shown that these two aspects are intimately linked and represent a
regulatory signalling pathway which can be exploited for vascular disease treatment.
There is compelling evidence for the involvement of voltage-gated T-type Ca2+ channels in VSMC
proliferation: in proliferating VSMCs, as L-type expression decreases, T-type expression
increases, and Ca2+ influx via T-type channels is required for VSMC proliferation in vitro and in
neointima formation observed following vascular injury. Most convincingly, murine knockout
models have recently shown beyond doubt that the T-type channel Cav3.1 is an absolute
requirement for VSMC proliferation following vascular injury and so represents an important
therapeutic target for the treatment of proliferative vascular diseases.
HO-1 induction affords protection in a variety of pathological cardiovascular conditions which all
involve VSMC proliferation. Indeed, HO-1 is established as anti-proliferative, and its induction is
observed in these diseases. Furthermore, evidence indicates CO accounts for such effects of HO1 in VSMCs yet the detailed mechanisms underlying HO-1/CO suppression of proliferation still
remain to be determined.
Our current studies, which show that CO is an important regulator of T-type Ca2+ channels has led
to our hypothesis that increased HO-1 expression, observed in proliferative vascular diseases,
regulates proliferation of VSMC via CO modulation of Cav3.1 channels. To address our
hypothesis fully, and examine the potential for exploiting this regulatory pathway for therapeutic
benefit, we have three specific major aims:
1) to define mechanisms of HO-1-derived CO modulation of VSMC Cav3.1 splice variants
2) to determine the consequences of such modulation on vascular remodelling in the systemic
vasculature using in vitro and in vivo approaches, and
3) to examine the potential beneficial effects of modulating the HO-1/CO/Cav3.1 signalling
pathway as a novel approach to treating proliferative vascular diseases.
Further details on our research related to this project can be found in these recent publications:
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Peers, C., Boyle, J.P., Scragg, J.L., Dallas, M.L., Al-Owais, M.M., Hettiarachichi, N.T.,
Elies, J., Johnson, E., Gamper, N., & Steele, D.S. (2015) Diverse mechanisms underlying
the regulation of ion channels by carbon monoxide. Br. J. Pharmacol. 172, 1546-1556.
Boycott,H.E., Dallas,M.L., Elies,J., Pettinger,L., Boyle,J.P., Scragg,J.L., Gamper,N., and
Peers,C. (2013). Carbon monoxide inhibition of Cav3.2 T-type Ca2+ channels reveals tonic
modulation by thioredoxin. FASEB J. 27, 3395-3407.
Hettiarachchi,N.T., Boyle,J.P., Bauer,C.C., Dallas,M.L., Pearson,H.A., Hara,S., Gamper,N.,
and Peers,C. (2012). Peroxynitrite Mediates Disruption of Ca(2+) Homeostasis by Carbon
Monoxide via Ca(2+) ATPase Degradation. Antioxid Redox Signal 17, 744-755.
Dallas, M.L., Yang, Z., Boyle, J.P., Boycott, H.E., Scragg, J.L., Milligan, C.J., Elies, J., Duke,
A., Thireau, J., Reboul, C., Richard, S., Bernus, O., Steele, D.S. & Peers, C. (2012) Carbon
monoxide induces cardiac arrhythmia via induction of the late Na+ current. Am. J. Resp. Crit.
Care Med. 186, 648-656.
Al-Owais, M.M.A., Scragg, J.L., Dallas, M.L., Boycott, H.E., Warburton, P., Chakrabarty, A.,
Boyle, J.P. & Peers, C. (2012) Carbon monoxide mediates the anti-apoptotic effects of heme
oxygenase-1 in medulloblastoma DAOY cells via K+ channel inhibition. J. Biol. Chem. 287,
24754-24764.
Peers, C. & Steele, D,S. (2012) Carbon monoxide: a vital signalling molecule and potent
toxin in the myocardium. J. Mol. Cell. Cardiol. 52, 359-365.
Research Environment
The research to be undertaken falls within the interests of the Multidisciplinary Cardiovascular
Research Centre (MCRC), of which the Principal Investigators are members. The MCRC is an
ambitious strategy for discovering causes and treatments of heart disease. It transcends
traditional scientific and departmental boundaries to bring the full weight of the UK's second
largest university and the city of Leeds teaching hospitals to bear on the primary reason for
premature death and disability in westernised societies. MCRC's mission is to advance
understanding of cardiovascular disease and thereby improve human life. It has particular focus
on: (1) Revealing mechanisms of vascular disease and associated changes in the myocardium for
the generation of therapeutics; (2) Using engineering and other fundamental disciplines to find
innovative approaches for cardiovascular diagnosis and protection; and (3) Developing new
investigators. The grouping embraces a large community of young people, postdoctoral research
fellows and students, working on a number of individual and collaborative projects with dynamic
scientific and social interaction both within and outside of the traditional Faculty boundaries.
Facilities
Among many facilities available within FOMH/FBS at Leeds is the cutting edge equipment such as
high-throughput automated patch-clamp system, bio-imaging facilities, proteomics etc. More
about the facilities and equipment available that will be used for this particular research project can
be found at http://www.fbs.leeds.ac.uk/facilities/index.htm.
Main Duties and Responsibilities of the Post
 To perform electrophysiology (patch-clamp, current clamp) on vascular myocytes as well as
recordings from immortalised cell lines transfected with ion channels/receptors of interest
(often in conjunction with pharmacological analyses)
 To perform Live fluorescent imaging, routine biochemistry and molecular biology
 In vivo studies will be conducted following training, and under close supervision.
 To design and conduct a programme of investigation in consultation with the principal
investigators, as appropriate, managing individual components of the study from the start of the
project to dissemination of findings within set timeframes.
 To generate and pursue independent and original research ideas in the appropriate subject
area
 To evaluate methods and techniques used and results obtained by other researchers and to
relate such evaluations appropriately to their own work
 Contribute to supervision and instruction of other members of staff, in particular, junior
researchers
 Present research results within the research group and the institute and through publication or
other recognised forms of output, e.g. peer-reviewed journals, reports and conference
presentation at local and national level.
 Analyse and interpret the results of own research and help to generate original ideas based on
outcomes.
 Be aware of the health and safety risks in the work environment and contribute to COSSH
assessments as appropriate
 Build on internal and external contacts and participate in networks for the exchange of scientific
information
 Perform research tasks independently, analyse data and communicate results within the
research group
 Keep abreast of relevant literature and maintain a good knowledge of the background and
current developments in the field of the project.
 Contribute to the productivity of the research team using creativity to help develop new
research ideas, programme design, and contribute to problem solving.
Relationships
The post-holder will report to Professor Christopher Peers in the Leeds Institute of Cardiovascular
& Metabolic Medicine (LICAMM), through whom he/she is responsible to the Head of Division of
Cardiovascular & Diabetes Research, and through them to the Head of Institute, and to the Dean
of the Medical School, and ultimately the Dean of the Faculty.
University Values
All staff are expected to operate in line with the university’s values and standards, which work as
an integral part of our strategy and set out the principles of how we work together. More
information about the university’s strategy and values is available at
http://www.leeds.ac.uk/comms/strategy/.
Person Specification
Essential
 A PhD in either physiology, pharmacology, biochemistry (or a related area) - applications will
be accepted from individuals who are nearing completion of their PhD, or who have already
submitted their thesis. In such cases any offer would be made subject to successful PhD
completion within a specific timeframe.
 Demonstrable experience in molecular biology & biochemistry techniques (e.g.
electrophysiological, imaging, biochemical, molecular-biological and in vivo studies)
 Demonstrable background knowledge of contemporary research in cardiovascular ion
channel physiology
 Demonstrable experience in patch-clamp electrophysiology
 Demonstrable experience of successfully using technically sophisticated equipment (e.g.
patch-clamp amplifiers, micromanipulators and associated software)
 Evidence of high quality research output (eg publications) and evidence of leadership of a
high-impact, peer-reviewed publication
 Demonstrable experience of maintaining accurate laboratory notebooks professionally to
underpin publications
 Evidence of effective interpersonal skills, with the ability to present well reasoned arguments
 Evidence of strong verbal and written communication skills – with the proven ability to
summarise research outputs/plans clearly and concisely in written reports (supported in full
by experimental data in publishable format)
 Evidence of excellent organisational skills, experience of managing own workload and an
ability to work to multiple deadlines
 Demonstrable research project management skills and experience
 A sustained and demonstrable record of innovative problem solving
 Previous experience of supervising junior staff and students
 Experience of working effectively and responsibly as part of a team on a collaborative
research project
 A proven aptitude for learning new skills and approaches
 Knowledge and experience in using appropriate computing and software
Desirable
 An interest in the field of cardiovascular ion channel regulation & modulation
Further Information
Faculty Information
With more than 6,000 students, 1,600 staff and annual research income of £50m, the Faculty of
Medicine and Health at Leeds is bigger than some universities. Leeds has one of the largest
medical and bioscience research bases in the UK, and is an acknowledged world leader in cancer,
cardiovascular, psychiatric, genetic, musculo-skeletal and health services research. Treatments
developed in Leeds are transforming the lives of people around the world living with conditions
such as HIV, TB, diabetes and malaria.
The School of Medicine
The School of Medicine at the University of Leeds is a major international centre for research and
education. Our ambition is to improve health and reduce health inequalities, locally and globally,
through excellent scientific research and the translation of that research into healthcare practice,
and through the education of future scientific and clinical leaders who will advocate and practise
an evidence-based approach. Our major strategic aims are to:
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Deliver outstanding research including basic discovery science through to applied health
research that makes a significant difference to health.
Produce exceptional graduates, clinicians, educators, doctoral and post-doctoral fellows
whose learning has been informed and inspired by our research excellence and who will
form the next generation of academic and clinical leaders.
Develop and support knowledge transfer activities that flow from our academic activities.
Create and maintain an efficient and sustainable environment for research and teaching
within an organisational culture and management style that enacts and supports the
university’s core values of community, inclusiveness, integrity and professionalism.
The School of Medicine is organised into seven Institutes. All are committed to high quality
research-led teaching, through their training of postgraduate research students, delivery of
postgraduate taught courses, and its leadership in undergraduate teaching. The School works
closely with the local NHS, having a number of jointly funded clinical posts to ensure this
relationship is effective and strong for both research and student education.
Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) Director: Professor
Mark Kearney
LICAMM integrates basic and clinical scientists with a common goal of understanding the
mechanisms underpinning common chronic diseases of human health and developing new
approaches to treating patients at an individual and population level. At the heart of LICAMM’s
philosophy is a vibrant multidisciplinary approach to science that provides a platform to deliver
internationally competitive translational research and teaching in disorders including
cardiovascular disease, diabetes, cancer and neurodegenerative diseases our key aim is to
improve the lives of our patients and the experience of our students.
Leeds Institute of Health Sciences (LIHS) Director: Professor Tim Ensor
LIHS delivers problem-driven research that supports decisions about the content or delivery of
healthcare. Our interdisciplinary approach incorporates expertise in applied health research
designs, health implementation sciences, social sciences, health economics, informatics and
statistics, as well as skills in communicating with basic scientists, policy makers, healthcare
providers, public and patients. We conduct research at the individual, population and
organisational level.
Leeds Institute of Medical Education (LIME) Director: Professor Trudie Roberts
LIME provides the administrative support, co-ordination and leadership for the School of
Medicine’s undergraduate medical degree, including admissions, curriculum development,
assessment, student support and clinical placement liaison. It provides the technology-enhanced
learning and innovation support for the School of Medicine. LIME also has a very active
scholarship programme of research and innovation in medical education and uses its expertise to
influence medical education policy and practice nationally and internationally. To achieve this it
works with a range of stakeholders including the academic community, the profession, the public,
regulators and policy makers.
The Leeds Institute of Cancer and Pathology (LICAP) Director: Professor Tim Bishop
The Leeds Institute of Cancer Studies and Pathology addresses both laboratory based and clinical
research into cancer with a major focus on translational science. LICAP is one of the largest
cancer institutes in the country and has major financial support from the cancer charities. The
laboratories and clinical research are all based on the St James’s site with laboratory activities
being located in the Wellcome Trust Brenner Building and adjacent buildings while the clinical
work is based within Bexley Wing.
Leeds Institute of Biomedical & Clinical Sciences (LIBACS) Director: Professor Philip
Hopkins
LIBACS undertakes clinically-driven research from the level of the gene through cellular, tissue
and organ to clinical trials. Our vision is to develop a sustainable centre of excellence for the
advancement of patient care by translating research results into clinical practise and contributing
to medical education at undergraduate and postgraduate levels. Our research interests are
encapsulated in 6 clinical themes (Gastrointestinal inflammation & tumorigenesis, Genetic
disorders, Infection & immunity, Neuroscience, Perinatal medicine, Perioperative outcomes &
technologies) underpinned by four generic science technology strands (Animal models, Cell
biology, Gene regulations & Genomics). We are based predominantly at the St James’s
University Hospital site.
Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM) Director: Professor
Paul Emery
LIRMM is dedicated to improving diagnosis, therapy, intervention and outcome across the
spectrum of rheumatic and musculoskeletal medicine. It boasts a dynamic portfolio of research
and education, delivering wide-ranging clinical, translational and basic research across five
Sections: Clinical Musculoskeletal Medicine, Experimental Musculoskeletal Medicine, Clinical
Biomechanics and Physical Medicine, Rehabilitation Medicine and Orthopaedics. A multidisciplinary approach is the core of our activities, with significant interdisciplinary links between
Experimental and Clinical research. LIRMM’s clinical activities are focussed at Chapel Allerton
Hospital, which is also base for our NIHR Musculoskeletal Biomedical Research Unit (LMBRU)
and our basic sciences at St James’s University Hospital.
Leeds Institute of Clinical Trials Research (LICTR) Director: Professor Julia Brown
LICTR delivers innovative design, delivery and knowledge transfer in clinical trials research. Our
multidisciplinary approach, in collaboration with basic scientists, clinicians, policy makers,
healthcare providers, public and patients and University colleagues, delivers internationally
competitive research and teaching that makes a significant contribution to the evidence base for
healthcare delivery. The Institutes research is conducted through the Clinical Trials Research Unit
where we have expertise in design and conduct of complex clinical trials incorporating novel
designs to evaluate CTIMPs, complex interventions, diagnostics, medical devices and surgery.
St James’s University Hospital Campus Infrastructure and Facilities (SCIF)
Director: Professor Pam Jones
This group covers activities that cover School of Medicine functions for Institutes at St James’s
University Hospital that span more than one institute including biomedical research facilities,
student education, IT, health and safety, estates, seminars, PGR studentships and business
support functions. These functions help support the five adjacent buildings on the site.
There are three Institutes with staff and students at St James’s: LICAP (Leeds Institute of Cancer
studies and Pathology), LIBACS (Leeds Institute of Biomedical and Clinical Sciences), LIRMM
(Leeds Institute of Rheumatic and Musculoskeletal Medicine). These three institutes are
dedicated to basic, translational, clinical and health research integrated with student education.
Additional Information
Terms and Conditions
Details of the terms and conditions of employment for all staff at the university, including
information on pensions and benefits, are available on the Human Resources web pages
accessible via the links on the right hand side, or at http://hr.leeds.ac.uk/policies.
University Teaching and Research Award
The Senate of the University has agreed that all newly appointed staff with a contract of 0.5 FTE
and above who have a teaching/ research role and are deemed new to teaching or research in
Higher Education should be required to complete successfully all of the requirements of the
University of Leeds Teaching and Research or an appropriate alternative. Whether or not this
applies to you, will be decided as part of the appointment procedure at interview.
Further details of the ULTRA are available at http://www.sddu.leeds.ac.uk/sddu-ultra.html.
Staff with contracts of less than 0.5 FTE may take the ULTRA provided that they have a broad
enough range of teaching, research and assessment to complete the requirements of the
Programme: this will be decided in conjunction with the School and the course providers.
Disclosure and Barring Service checks
A Disclosure and Barring Service (DBS) Check is not required for this position. However,
applicants who have unspent convictions must indicate this in the ‘other personal details’ section
of the application form and send details to the Recruitment Officer.
Disabled Applicants
The post is located in the Garstang Building. Disabled applicants wishing to review access to the
building are invited to contact the department direct. Additional information may be sought from
the Recruitment Officer, email disclosure@leeds.ac.uk or telephone + 44 (0)113 343 1723.
Disabled applicants are not obliged to inform employers of their disability but will still be covered
by the Equality Act once their disability becomes known.
Further information for applicants with disabilities, impairments or health conditions is
available in the applicant guidance.