Ongoing projects

A brief overview of ongoing research projects which are affiliated to the Insigneo Institute for in silico Medicine.

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Projects started in:

2020 

The role of the transcription factor TWIST 1 in the progression of atherosclerosis

Cardiac research in Sheffield has received a major boost from the British Heart Foundation (BHF) in the form of an £800,000 award to develop a new gene therapy to treat cardiovascular disease (CVD).

The BHF award to Insigneo Member Professor Paul Evans at the University of Sheffield’s Department of Infection, Immunity and Cardiovascular Disease (IICD) is for a project to identify a new drug treatment which will ‘switch off’ genes that promote CVD.

The renewal of the BHF Programme Grant will allow Professor Evans and two new postdoctoral early career researchers to explore the various mechanisms which cause atherosclerosis. This is a disease characterised by the accumulation of cholesterol-rich fatty material in the arteries that leads to angina, heart attack and stroke.

The team has identified a gene in the inner layer of the arteries of the heart (the endothelium) that is important in promoting the development of CVD. 

Professor Evans said: “We will be identifying a drug to target a gene which contributes to the build-up of fatty material in the arteries. Switching this gene ‘off’ will make the arteries in the heart less ‘leaky’, preventing cholesterol from building up and causing blockages which present as heart attacks and stroke.”

The highly collaborative project will see scientists from the University of Sheffield’s IICD and gene specialists from the Department of Neuroscience partner with national and internal research colleagues.

Start date: 3 April 2020

Find out more: Paul Evans Lab

The PORTRAIT study

Hypophosphatasia (HPP) is an inherited condition that leads to weak bones. Early childhood forms are severe and easily recognised. Adult forms can vary in severity.

HPP is often missed by doctors or confused with osteoporosis. This is important because the usual osteoporosis treatments may be harmful to patients with HPP and increase the risk of broken bones. One of the reasons it is missed is a lack of research describing the typical features of HPP, so doctors don’t recognise the signs, and don’t know when or how to test for it.

‘Clinical Consequences of Adults Presenting with Hypophosphatasia with Special Focus on Gait, Bone Microstructure and Cognition: The PORTRAIT study’ will help increase understanding of the burden of disease of HPP on patients.

The aim is to examine the effects of HPP on bone structure and strength, physical functioning, cognition, and quality of life. Researchers will study adults with HPP and healthy age-matched and gender-matched individuals. Blood samples will be collected after an overnight fast. Researchers will use these samples to measure markers of HPP and bone health.

Medical history and lifestyle, quality of life and cognitive function will be assessed using questionnaires. Bone mineral density, body composition and bone structure and strength will be measured using dual energy x-ray absorptiometry and high resolution peripheral quantitative computed tomography.

Physical functioning will be assessed as participants perform a series of physical performance and gait tests. Magnetic resonance images of the lower limbs will be matched-up with the physical functioning data to create patient-specific musculoskeletal models. Cognitive function tests will be performed to assess cognition and mental health.

To reveal the burden of disease of HPP, the data collected from patients with HPP will be compared to that collected from healthy controls.

This clinical trial is sponsored by Sheffield Teaching Hospitals NHS Foundation Trust and is led by Professor Richard Eastell with Professor Claudia Mazzà as co-investigator.

Start date: 15 January 2020

Find out more: The PORTRAIT Study

2019 

ISABELA Imaging Study

Assessment of lung function in patients with idiopathic pulmonary fibrosis using hyperpolarised xenon MRI, a sub-study of the ISABELA trial (funded by Galapagos).

Start date: 12 December 2019

Virtu-4 – A virtual study of modelled FFR in clinical practice

Fractional flow reserve (FFR) is ideal to guide treatment of coronary artery disease, but few receive it because it needs a pressure wire. We can compute a ‘virtual’ (v) FFR from the coronary angiogram without a pressure wire.

Hypothesis: vFFR could transform the management of patients undergoing coronary angiography.

Method: This is a ‘virtual’ trial of angiogram vs vFFR. vFFRs will be calculated based upon the angiogram. The Heart Team will formulate a treatment plan based upon the angiogram and the vFFR will then be revealed.

Impact: Change in treatment strategy with vFFR compared with usual care.

Start date: 1 November 2019

CompBioMed2 – A Centre of Excellence in Computational Biomedicine

CompBioMed is a European Commission H2020 funded Centre of Excellence focussed on the use and development of computational methods for biomedical applications.

Start date: 1 October 2019

Find out more: CompBioMed

PathAnalyse: Towards the redesign of outpatient services using visual process analytics

This project from Sheffield Teaching Hospitals NHS Foundation Trust aims to advance analytical capability using PathAnalyse – a tool to improve health care delivery at outpatient clinics using visual data analytics.

Start date: 1 September 2019

Find out more: PathAnalyse

METASPINE – Comprehensive experimental and computational mechanical characterisation of metastatic vertebrae

METASPINE will deliver, for the first time, a method to comprehensively evaluate the effect of the properties of lytic metastatic bone lesions on the mechanical competence of metastatic vertebrae. It will achieve this by combining state of the art experiments, imaging, image processing and computational modelling.

Start date: 1 September 2019

Find out more: Cordis EU

RESPIRE 3 – Free-breathing, rapid, multi-nuclear MRI of lung

Dr Neil J Stewart was awarded a European Respiratory Society (ERS) Global Marie Skłodowska-Curie Fellowship. He is working in the POLARIS group on the feasibility of hyperpolarised gas lung Magnetic Resonance Imaging (MRI) to assess infant lung disease.

The RESPIRE programme provides postdoctoral research fellowships to researchers with the potential to become the leaders of tomorrow in the respiratory field.

The RESPIRE3 and RESPIRE4 projects receive funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreements No 713406 and No 847462 (MSCA COFUND scheme).

Start date: 5 August 2019

Sano: A Polish Centre for Computational Medicine

Insigneo is a key partner in a major international initiative to establish a new Centre for Computational Medicine in Krakow, Poland.

Benefiting from favourable European funding initiatives, over the next seven-year period Sano will leverage around €32M of EC and Polish National support. This is to establish and expand a sustainable educational and translational facility serving Europe and beyond.

The project is led in Sheffield by Insigneo Director of Operations, Dr Andrew Narracott, and carefully designed to complement Insigneo’s more exploratory research activities. Sano’s focus is on the late-stage commercial/clinical implementation of in silico clinical support systems, offering opportunities for translational activities that may have relevance for Insigneo researchers.

Start date: 1 August 2019

Find out more: Sano

VIRTU-Q – Modelling volumetric coronary artery blood flow

Coronary artery disease, the world’s leading cause of death, is caused by a narrowing in the arteries of the heart.

Patient’s treatment is most effective when based upon how much these narrowings restrict blood flow. This is challenging to measure, and rarely done, resulting in uncertain treatment decisions in around a third of patients.

Dr Paul Morris has devised a computational method that accurately measures coronary blood flow during routine assessment. It requires no additional equipment, risk or expense, and enables ‘small vessel’ heart disease to be diagnosed; a common and important condition which is frequently missed altogether.

Start date: 1 August 2019

Multi-band optical coherence tomography platform for the development of novel atopic dermatitis treatments

This project is a unique partnership between clinicians, engineers and drug companies which will develop cutting edge Optical Coherence Tomography tools and assess their effectiveness in assessing new Atopic Dermatitis treatments.

Start date: 1 July 2019

Find out more: ESPRC

MultiSim2 – Frontier Engineering: Progression Grant in Modelling complex and partially identified engineering problems. Application to the musculoskeletal system

MultiSim2 will develop new approaches for better imaging, characterisation and modelling of the muscles and of their interaction with the skeletal system.

Start date: 1 June 2019

Find out more: Multisim Insigneo

EDiMplant – Electrical Discharge Machining for enhanced osseointegration and antibacterial capabilities of β-phase Titanium Implant

To ensure the long-term survival of orthopaedic implants, it is urgent to tailor a multifunctional surface which would simultaneously have enhanced osteogenic and antibacterial properties.

The aim is to develop a competent surface modification technique which will promote improved osseointegration whilst retaining antimicrobial activity, thus ensuring the life-long performance of implants. 

A novel surface modification approach will be demonstrated using the specially designed tool electrodes in powder mixed electric discharge machining process for fabrication of modified surface layers exhibiting anti-bacterial and osteogenic characteristics.

Start date: 1 June 2019

Find out more: Cordis EU

Lung MRI for risk stratification

Researchers, led by Professor Matthew Hatton at Sheffield Teaching Hospitals NHS Trust and Professor Jim Wild and Dr Bilal Tahir at the University of Sheffield, will use the city’s world-leading magnetic resonance imaging (MRI) centre to produce revolutionary pictures of cancer patients’ lungs before they begin treatment.

These more advanced MRI images will be analysed to determine how well the patients’ lungs work and how likely they are to recover well from surgery. This could help doctors select the best treatment for their patients.

Start date: 1 June 2019

Find out more: Yorkshire Cancer Research

Mobilise-D – Connecting digital mobility assessment to clinical outcomes for regulatory and clinical endorsement

Mobilise-D brings together clinicians, scientists, prominent academic centres, businesses, and the world’s largest pharmaceutical and medical industries to revolutionise assessment of mobility loss. This is achieved using digital technology, leading to a game changer for clinical trials and clinical management of mobility.

Start date: 1 April 2019

Find out more: Mobilise-D

SPOT – Skin Pathology assessment with Optical Technologies (SPOT): a cross-sectional clinical study in atopic dermatitis patients and healthy subjects

This fundamental research project is the first in a series of studies investigating new imaging technologies for the non-invasive monitoring of atopic dermatitis treatment effects.

Start date: 1 February 2019

PRIMAGE – PRedictive In-silico Multiscale Analytics to support cancer personalized diaGnosis and prognosis, Empowered by imaging biomarkers

PRIMAGE is a €7.2m integrated project funded under the EU Horizon 2020 Programme and proposes a cloud-based platform to support decision making in the clinical management of malignant solid tumours, specifically neuroblastoma, offering predictive tools to assist diagnosis, prognosis, therapies choice and treatment follow up. The methodologies developed by the project consortium will include the use of novel imaging biomarkers, in silico tumour growth simulation, advanced visualisation of predictions and generation of machine-learning based predictors for the most relevant, disease-specific, clinical end points, with the aim of improving patient diagnosis, treatment and reducing costs.

At the University of Sheffield, we will be responsible for developing a cellular level agent-based model (ABM) of the neuoblastoma tumour microenvironment, led by Dr Dawn Walker in the Department of Computer Science, working with Insigneo PDRA, Dr Kenneth Wertheim, and collaborators at the University of Bologna to integrate this into a multiscale model from molecular to organ level and also optimising this model and deploying it in a HPC environment, led by Dr Paul Richmond in the Department of Computer Science.

Start date: 08/01/19

Find out more: https://www.primageproject.eu/project/

2018

Assessment of structural and functional lung MR imaging in the monitoring of treatment in IPF

Investigation into prognostic indicators of Idiopathic Pulmonary Fibrosis (IPF) using structural-functional pulmonary MRI assessment.

This study involves patients with the condition idiopathic pulmonary fibrosis (IPF), which causes lung scarring. The study aims to discover more about the role of Magnetic Resonance Imaging (MRI) in these patients. The patients have MRI scans and breathing tests over a period of 12 months to assess this.

Start date: 1 December 2018

Find out more: POLARIS

HUSH – Hearing Aids for Tinnitus with Hearing Loss

Feasibility of conducting a multi-centre randomised controlled trial to assess effectiveness and cost-effectiveness of digital hearing aids in patients with tinnitus and hearing loss.

Start date: 1 October 2018

Find out more: Dimensions

Hypo-RESOLVE – Hypoglycaemia – Redefining SOLutions for better liVEs

Hypo-RESOLVE works on new solutions to handle hypoglycaemia in diabetes for the benefit of people worldwide.

The project aims to provide researchers and clinicians with more validated data about the condition by

  • creating a sustainable clinical database
  • conducting studies to better understand the underlying mechanisms of hypoglycaemia
  • conducting a series of statistical analyses to define predictors and consequences of hypoglycaemia
  • calculating the financial cost in European countries

Start date: 1 May 2018

Find out more: Hypo-RESOLVE

The role of c-REL in focal endothelial dysfunction and atherosclerosis

This study will look at at whether ‘turning off’ a protein could help prevent heart attacks and strokes. Professor Paul Evans will look at the role a protein called c-Rel plays in the development of atherosclerosis.

Previous research found that a protein, known as c-Rel, is ‘switched on’ by damage to the blood vessel walls, and accelerates the build-up of fatty plaques even further. In this study, Professor Evans will investigate how removing c-Rel affects the progression of the disease in mice.

Start date: 19 February 2018

Find out more: BHF News

STriTuVaD – In silico Trial for Tuberculosis Vaccine Development

The STRITUVAD project aims to develop computer simulations to test the efficacy of new therapies, significantly reducing costs and duration of human clinical trials.

Start date: 1 February 2018

Find out more: STriTuVaD

SPINNER – SPINe: Numerical and Experimental Repair Strategies

The aim of SPINNER is to train Bioengineering early stage researchers to be in a position to design the next generation of repair materials and techniques for spine surgery.

Start date: 1 January 2018

Find out more: Spinner EID

2017

VPM2 – In silico approaches for preclinical assessment of bone changes in osteoporosis and osteoarthritis studies

This project aims to improve the current preclinical assessment of interventions for bone diseases such as osteoporosis, OP, and osteoarthritis, OA. This is by developing more accurate longitudinal measurements in mice and evaluating endpoints, which are more relevant to predict the outcomes of the treatment in patients, and therefore facilitate the clinical translation.

Start date: 1 December 2017

Find out more: NC3RS

Determining Novel SMURF1 Signalling Pathways and Precision Medicine Strategies in Patients with Pulmonary Arterial Hypertension

Dr Alexander Rothman will examine how SMURF1 functions in disease using biological techniques and new SMURF1 targeted drugs.

Start date: 6 November 2017

Find out more: Wellcome Funding

Development and application of multi-modality image processing methods for quantitative structural and functional understanding of lung diseases

Start date: 1 October 2017

Wellcome Trust – Clinical Research Training Fellowship. Pulmonary Vascular Disease: Computational Modelling and large data analytics

Investigating pulmonary hypertension using computer-based methods to combine information from MRI and CT scans into models, to improve patient diagnosis and prognosis.

Start date: 7 August 2017

CIMA – Centre for Integrated research into Musculoskeletal Ageing (CIMA) Renewal

The MRC-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA) was formed in 2012. It has developed an integrated approach to studying the effects of ageing on the musculoskeletal system, which has been demonstrably successful.

Start date: 1 June 2017

Find out more: CIMA

Uncertainty Quantification in Prospective and Predictive Patient Specific Cardiac Models

This project will apply the mathematics of uncertainty quantification, developed for automotive, geological and meteorological predictions, combined with biophysical models of individual patient physiology and pathophysiology to predict patient outcomes and their corresponding probabilities.

Start date: 1 May 2017

Find out more: UK Research and Innovation

YCR CONNECTS – Yorkshire Cancer Research (YCR) Catalyst for Innovation in Cancer Care and Treatment in Sheffield

To improve cancer outcomes in Yorkshire and beyond through research and innovation.

YCR CONNECT aims to

  • develop and implement new cancer treatments
  • improve cancer outcomes in Sheffield and ensure patients live longer and enjoy better quality of life
  • integrate the many existing facets of world leading cancer research in Sheffield into patient focused innovations in cancer care
  • attract high quality researchers and cancer specialists to Sheffield
  • promote increased external investments into cancer research in Sheffield
  • train the academic workforce of the future for cancer research and care in Sheffield
  • build further cancer research collaborations within Yorkshire and beyond

Start date: 1 April 2017

Find out more: YCR Connects

National Institute for Health Research (NIHR) Sheffield Biomedical Research Centre (BRC) for Neuroscience

A research partnership between the University of Sheffield and Sheffield Teaching Hospitals NHS Foundation Trust, dedicated to improving the treatment and care of people living with chronic neurological disorders.

The Sheffield Biomedical Research Centre is focused on translational neuroscience for chronic neurological disorders.

Start date: 1 April 2017

Find out more: NIHR Sheffield Biomedical Research Centre

TRISTAN V3 – Translational Imaging in Drug Safety Assessment

The objective of the project is to validate Translational Imaging in Drug Safety Assessment.  The consortium will use imaging techniques to improve drug safety analysis.

This needs thorough validation of imaging procedures as “biomarkers”. This will help drug developers to bring new, safer drugs to the market and thereby enable doctors to treat their patients more effectively.

Start date: 1 January 2017

Find out more: Tristan

2016

The cortical representation of low-probability stimuli and its neuromorphic implementation

This project will investigate the biophysical mechanisms of stimulus-specific adaptation (SSA) as well as its implementation on neuromorphic analogue circuitry.

Start date: 5 September 2016

Find out more: Wellcome Funding

MICA – Non-invasive quantitative ventilation imaging by MRI of fluorocarbon gases

Developing non-invasive and radiation-free imaging of lung ventilated volume, using new MRI technologies.

Start date: 3 August 2016

Find out more: UK Research and Innovation

Developing and trialling the DAFNEplus (Dose Adjustment for Normal Eating) intervention. A lifelong approach to promote effective self-management in adults with type one diabetes

To re-develop and evaluate the DAFNE programme to help people with type one diabetes to better manage their condition in line with their lifestyle.

Start date: 1 March 2016

Find out more: DAFNEplus

Accelerating Scientific Discovery with Accelerated Computing

Revolutionise the use of High Performance Computing (HPC) within the University of Sheffield. Achieved by changing perceptions of how people utilise software and are trained and supported in writing code which scales to increasingly large computer systems.

Start date: 1 February 2016

Find out more: UK Research and Innovation

2015

Polaris – Expansion of state-of-the-art MR imaging infrastructure for pulmonary disease stratification

Polaris focuses on the physics and engineering methods for lung imaging with proton and hyperpolarised gas MRI, and their clinical applications.

Start date: 1 April 2015

Find out more: POLARIS

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