MRes Cardiovascular Medicine: From Molecules to Man course structure information

A medical research laboratory
Research Skills (15 credits): CDL602

Module Leader – Dr Janet Chamberlain

This module will develop your research skills in order to equip you with the necessary expertise needed to gain the most from both the taught components of the course as well as the Research Project. The module covers aspects such as information literacy, oral presentation skills, scientific writing, critical analysis skills, data analysis and presentation, statistics and basic laboratory techniques.

During the module you will develop your information retrieval skills using a variety of appropriate sources in order to select and recover relevant recent primary papers on a topic. You will also develop the ability to critically evaluate the quality of published scientific literature. Both oral and written presentation skills will be developed through the production of a well-structured critical analysis of a a media article and related published papers that will be presented to academics and peers. In addition, you will spend some time in the laboratory learning some basic skills and the theory behind them as well as basic data handling, presentation and statistics (using Prism).

Teaching Methods:

Lectures, tutorials, discussions, laboratory practicals, demonstrations.

Assessment:

Critique of published media and research articles. In silico project report, or wet lab project report.

Vascular Cell Biology (15 credits): CDL401

Module Leader - Dr. Heather Wilson

This module explores the molecular mechanisms underlying cardiovascular disease and introduces the students to basic knowledge on which the remaining pathway modules are based. There is a strong emphasis on inflammation and the role it plays in cardiovascular disease, an area that is highly relevant to the development of new therapies as demonstrated by the recent CANTOS trial. The module builds upon the research in the Department of Infection, Immunity and Cardiovascular Disease, exploring the cellular mechanisms, molecules and signalling pathways involved in the pathology of vascular diseases.

The module incorporates a laboratory experience; students will gain hands-on experience of cell biology methods that we use to understand vascular biology function. There is a strong emphasis on using experimental approaches to test hypotheses and an ability to apply background knowledge to assess experimental results.

Teaching Methods

You will be given lectures, take part in tutorials and carry out practical laboratory work.

Assessments

You will write an extended abstract and present a poster to Academics and peers.

Vascular Disease - Models & Clinical Practice (15 credits): CDL402

Module Leader - Dr. Victoria Ridger

This module builds on the basic cellular and molecular principles learnt in the previous module. We examine the value of in vivo model systems, including zebrafish, in testing hypotheses, and the development of classical and emerging therapies is explored. There is a strong emphasis on the need to consider the 3Rs – replacement of animal models with in vitro and in silico models that can yield meaningful and insightful data; reduction in numbers of animals used and refinement of models through careful experimental design as well as screening using in vitro and in silico models prior to the use of animals. Students will visit the Bateson Centre to observe experimental procedures using zebrafish carried out in the labs of Professor Tim Chico.

The module also examines how basic science is translated into clinical practise and therapy. We cover global epidemiology, drug treatment and clinical intervention and consider relevant ethical issues. Students will have the opportunity to visit the Cardiovascular and Cardiology clinical departments, the Clinical Research Facility and to observe a current clinical interventional technique in the Cath Labs at the Northern General Hospital.

Teaching Methods

Lectures, tutorials and discussions, visits to laboratories, clinical research facilities and clinical departments.

Assessments

You will write a short journalistic report in the style of Scientific American and produce handouts for a presentation you will give on a “first in man” study.

Critical Review (15 credits): CDL601

Module Leader - Professor Sheila Francis

This module aims to develop your ability to retrieve information from appropriate sources, and synthesise and critically analyse published literature. It follows on from the information literacy training you will receive in CDL602. The subject of your critical review is linked to your research project, which you will have chosen immediately prior to the start of this module. You will write a review of the recent literature on the background to your future laboratory research project, as if it were intended for publication as a short review article or as the background section of a grant application.

Much of the work on this module is self-study but you will meet with your Project Supervisor to discuss a first draft and then a final draft before submission. As well as developing your skills at information retrieval, critical evaluation of published literature and how to identify appropriate publications to develop and evidence-based scientific position, it provides a firm foundation of knowledge on which to start you Research Project.

Teaching Methods

Tutorials as well as individual meetings with your Project Supervisor.

Assessment

Review of approximately 3000 words.

Research Project (120 credits): CDL603

Module Leader – Dr. Rachid Tazi-Ahnini

The research project provides the opportunity to learn and apply research methods to test a specific scientific hypothesis using the knowledge gained in the previous taught modules of the course. A list of projects will be made available at the start of the course, where students are offered the opportunity to discuss and select their projects. We encourage students to engage with designing the project in collaboration with the Project Supervisor. The student will have significant input into the design of the research and will be expected to have developed sufficient skills to carry out aspects of their project independently over time. The project takes place over 30 weeks, incorporating an oral presentation and culminating in the production of a dissertation detailing the research findings and placing the work within a greater scientific context.

Students will join in with departmental seminars, research group meetings, journal clubs and supervisor meetings, to learn and experience the role of a scientific researcher, by undertaking hypothesis-led research.

Teaching Methods

Tutorials and regular meetings with your Project Supervisor as well as initial day-to-day supervision by the Supervisor or member of the research team/group.

Assessment

Abstract, presentation and dissertation (20,000 – 30,000 words) describing the Research Project.

Projects

The research project forms the major part of your studies. Here are some examples of the types of projects that may be available:

Modelling blood flow to improve the management of coronary artery disease.

Supervisor: Professor Julian Gunn

In order to develop an accurate model of blood flow in patients with coronary artery disease (CAD) you will: 1. learn about decision making in the management of CAD. 2. Learn about the physiology of coronary blood flow in health and disease, including fractional flow reserve (FFR). 3. Familiarise yourself with our VIRTUheart model of virtual (computed) FFR. 4. Work on improving accuracy of the model. We have a wealth of clinical data (angiograms and measured FFRs) in our research archive (ArQ). You will have full access to these data and will be able to process the angiograms in the VIRTUheart software and produce your own measures of virtual FFR for your individual project. This will include aspects such as investigating the effect of branched vessels, diffuse disease, chronic occlusions, grafts, vascular distensibility, myocardial ischaemic burden, acute coronary syndromes and 'virtual' stunting. You will be taught about coronary anatomy, angiography, angioplasty, bypass surgery, image processing, using software tools, data analysis and report writing.

Investigating a novel anti-inflammatory role for statins through modulation of neutrophil microvesicle production.

Supervisor: Dr. Victoria Ridger

Cardiovascular diseases (CVD) account for 31% of all global deaths. Atherosclerosis, an accumulation of fibro-fatty plaques in the vessel wall, is a major underlying cause of CVD. High cholesterol levels are a risk factor for developing atherosclerosis and lipid-lowering statins decrease plaque progression. However, statins also have effects beyond cholesterol lowering, including modulation of microvesicle production. Microvesicles are membrane-derived sacs released from cells, which contain cellular material and express molecules derived from the parent cell. Neutrophil microvesicles exacerbate vascular inflammation in atherosclerosis by activating endothelial cells through delivery of their cargo, including microRNA.
This project will investigate whether statins can modulate neutrophil microvesicle function by inhibiting their release or altering their content. The project will involve cell isolation techniques, tissue culture, flow cytometry, qPCR, ELISA, immunoblotting and immunocytochemistry.

Serological and imaging biomarkers in the assessment of right ventricular failure in pulmonary arterial hypertension.

Supervisor: Dr. Andy Swift

Pulmonary arterial hypertension is a severe disease associated with poor outcome due to failure of the right ventricle. Reliable monitoring of the right ventricle and identification of right ventricular failure is crucial to deliver the optimal therapeutic approach. Specific serological biomarkers have been identified as useful prognostic markers particularly at follow up, strongly predicting all-cause mortality. In addition, several novel serological biomarkers are emerging with great potential for both diagnosis and prognostic in PAH. Magnetic resonance imaging is considered the gold standard test for evaluation of the right ventricle. The ambition of this research is to determine the clinical value of serological biomarkers and compare with MRI in patients with PAH. This study will include exposure to lab-based and clinically applied research; the student will be required to develop core lab skills coupled with competency in cardiopulmonary MRI analysis.

The role of a novel inflammatory macrophage marker in human immunity responses.

Supervisor: Dr. Heather Wilson

In the artery wall, macrophages play an important role in driving atherosclerosis, by taking up lipid and forming the necrotic lipid core that builds plaque deposition. Macrophages show plasticity between different states or phenotypes, according to their functions in: the inflammatory response to infection; in clearing pathogens; and in the resolution and repair response following injury or infection. In order to analyse how macrophages change within diseased arteries we discovered a novel membrane protein marker for the inflammatory phenotype. This project will build our understanding of the function of this novel membrane protein. We hypothesise that this protein is involved in the inflammatory macrophage response to lipid uptake, phagocytosis and pathogen sensing. You will perform siRNA knockdown of this protein in human monocyte-derived macrophages, to assess its role in phagocytosis, pathogen clearance and lipid loading.

Investigating the role of Filamin A in Pulmonary arterial hypertension.

Supervisor: Dr. Allan Lawrie

Cytoskeletal proteins that binds to actin to cross-link actin filaments, and can also act as a protein scaffold for numerous protein partners. Mutations in specific cytoskeletal proteins are associated with severe arterial abnormalities, and through whole genome sequencing we have recently identified causal mutations in patients with Idiopathic Pulmonary Arterial Hypertension (IPAH). How these mutations link to the molecular and cellular pathogenesis of IPAH is unknown. You will investigate the expression and function of these genes in pulmonary artery smooth muscle cells and endothelial cells from patients with IPAH and controls as well as lung tissue from rodent models and post-transplant heart and lungs.

Investigation into the effects of ticagrelor on plasma adenosine levels.

Supervisor: Professor Rob Storey

The PLATO study demonstrated that ticagrelor, a platelet P2Y12 receptor antagonist, reduced mortality in patients with acute coronary syndromes (ACS) compared to standard therapy with clopidogrel. While it is well established that ticagrelor results in higher and less variable platelet P2Y12 inhibition than clopidogrel, it is hypothesised that the observed effect on mortality rates may relate to additional effects of ticagrelor. These off-target effects of ticagrelor may be attributable to its ability to selectively inhibit adenosine uptake by erythrocytes via equilibrative nucleosidase transporter 1 (ENT1) and inhibit platelet-expressed ENT1. Inhibition of ENT1 may result in increased plasma adenosine levels. Studies looking at plasma adenosine levels following ticagrelor therapy have shown conflicting results; an increase in plasma adenosine has been observed in patients with ACS and peripheral vascular disease but a study in healthy volunteers and a study carried out in Sheffield in patients undergoing elective coronary artery stenting have shown no effect. This research project will obtain additional information on the effect of ticagrelor on plasma adenosine levels and identify potential explanations for the discrepancies observed between clinical studies.

Hemodynamics of stents and effects on vascular healing.

Supervisor: Profesor Paul Evans

Stents alter local flow patterns which have major effects on inflammation, vascular dysfunction and restenosis. To understand the molecular mechanisms linking flow to vascular function you will use state-of-the art cell culture and molecular biology techniques to elucidate the effects of flow on coronary artery endothelial function. This will include the use of unbiased microarray/RNAseq omics approaches coupled to gene silencing technology to assess the function of flow-sensitive genes. The project will equip you with modern molecular techniques that are required for postgraduate molecular medicine research at the PhD level.

Computer Modelling In Treatment Management of Patients with Aortic Valve stenosis

Supervisor: Norman Briffa

Aortic valve stenosis is the most common valvular disease in the UK and its prevalence is rising with an ageing population. Symptomatic patients have a poor prognosis and the only effective treatment is aortic valve replacement (AVR). This can be performed during open heart surgery or in certain cases using transcatheter techniques. Symptomatic and haemodynamic improvement (decrease in gradient and myocardial work) after AVR is dependent on several factors including size and type of the implanted prosthesis and function of the left ventricle. Computer modeling and artificial intelligence (AI) are increasingly being used in medicine to help physicians make diagnoses and/or choose appropriate treatments. Using a computer model that was developed by the Eurvalve project, we hope to predict both the degree of change in both haemodynamics, cardiac work and symptoms that will occur after AVR.

Validation will take place using data from patients who already have received their treatment and the model will be used prospectively in 20 patients with aortic stenosis undergoing treatment.

The role of RNA editing in the pathogenesis of pulmonary arterial hypertension

Supervisor: Dr Roger Thompson

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by vascular remodelling that leads to increased resistance in the pulmonary circulation, right heart failure and premature death. The bone morphogenetic protein (BMP) signalling pathway is strongly implicated in disease susceptibility, with mutations in the BMPR2 gene found in approximately 15% of patients with idiopathic disease and over 70% of patients with the heritable form of the disease. Reduced BMPR2 signalling in the absence of mutations has been widely reported in patient cells and tissue and in animal models of pulmonary hypertension, but how signalling is suppressed in this context remains unclear. RNA editing is a post-transcriptional modification that promotes transcriptional diversity across tissues and can alter protein translation, stability, structure or function. Compelling evidence has emerged to implicate adenosine-to-inosine (A-to-I) RNA editing in vascular biology by ADAR1, the master regulator of A-to-I editing in vascular cells; however, the roles of these pathways have not been examined in PAH. The goal of this project is to determine whether ADAR1 regulates pulmonary vascular remodelling.

Four-dimensional flow cardiovascular magnetic resonance imaging (4D flow CMR) for Precision Medicine

Supervisor: Dr Pankaj Garg

We have several themed projects which involve cutting-edge 4D flow technology to improve diagnosis and guide therapy in cardiac disease. The projects involve enhanced evaluation of valvular heart disease, heart failure and pulmonary hypertension using 4D flow CMR. Sheffield is uniquely positioned to offer these opportunities as we have a high computational lab at the Imaging Sciences lab located in POLARIS.

This project will equip the students with the following skills:

  • Advanced critical insight into cardiovascular physiology using imaging-based methods
  • Segmentation of heart MRI for deriving physiologically relevant functional and tissue characterisation parameters
  • Understanding of software solutions for heart MRI analysis
  • IT skills including collaborative writing, handling referencing software, visualisation and curation of large datasets

The student will be expected to publish at least 2 papers from this project under the supervision of Dr P Garg and Dr A Swift. They will be encouraged to present their findings at national/international conferences. 


See full course information on our Prospectus

The content of our courses is reviewed annually to make sure it is up-to-date and relevant. Individual modules are occasionally updated or withdrawn. This is in response to discoveries through our world-leading research, funding changes, professional accreditation requirements, student or employer feedback, outcomes of reviews, and variations in staff or student numbers. In the event of any change we'll consult and inform students in good time and take reasonable steps to minimise disruption.

Information last updated: 17 September 2020


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