CTI Research Themes

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CTI Research
Themes

Translational cell biophysics

Collinson L and Larijani B - The Francis Crick Institute and University of Bath

Structure-function of proteins controlled by immune related lipid signalling events, affected by membrane morphology

The main objective of this theme is to investigate the structure-function of various proteins involved in inflammation and immune cell activation pathways, particularly those controlled by lipid signalling events and how they are affected by membrane morphology. This will be in relation to localised intervention of small molecules and/or macromolecules with the aim of transforming the activation states of the proteins involved for application in pharmaceutics.

The implementation of membrane biophysics is essential to the functional targeting of therapeutics to subcellular compartments in models of immuno-oncology and immune pathology. The functional targeting is dependent on physical properties of the membranes to which proteins interact with/bind, such as membrane curvature and localised molecular order, which themselves are primarily determined by lipid composition. Thus, it is imperative to characterise these physical properties non-invasively in the living cells; this is where advances in the underlying physics/biophysics techniques will make a critical difference. The relationship between membrane structure alterations, via lipid synthesis pathways will be interrogated. High throughput image recognition, pathway analysis of global patterns resulting from the functional proteomics and lipidomics will be utilised in this research theme. It will also include the determination of structural activity-relationships of possible new medicines designed to target the sites of dysregulation in the signalling network of inflammation, oncology, and immune pathologies.

A second objective is the inference of intracellular parameters that control the membrane voltage dynamics of biological cells from observations of macroscopic quantities, such as membrane voltage oscillations which are accessible to the experimentalist. This method allows building quantitative models of individual neurons and functional neuronal networks from in-vitro electrophysiological recordings and in-vivo time series observations of functional networks. This approach has successfully predicted the response of small neural networks to arbitrary stimulation. It has also allowed small bioelectronic implants to be designed that adapt to physiological feedback to cure chronic diseases thus developing novel therapies. Some of these devices are exploited by University start-ups. The methods may also function as a diagnostic tool to identify anomalous properties of ion channel proteins and optimise the effect of drugs in Alzheimer’s diseases and channelopathies.

Professor Banafshe Larijani

Professor Alain Nogaret

Mechanisms of disease and regeneration: routes to new immune-biotherapeutics

Tosh D and Ward SG- The University of Bath

Our focus is to understand the molecular pathways responsible for developmental and physiological processes at cellular and organismal level. We study function with methods ranging from single cells, tissue and organs, through to whole-body physiological performance and detailed systems biology and omics technologies. Such knowledge allows us to identify how dysregulation of molecular and cellular processes leads to disease and how they can be manipulated to repair or regenerate tissue and/or function.

The theme seeks to develop not only detailed mechanistic insight but also new therapeutics that include traditional small molecule chemical entities, but better also harness the new field of “biologic” medicines that span vaccines, monoclonal antibodies (and their variants) and cell-based therapeutics such as stem cells.

Our expertise spans pharmacology, biochemistry, immunology as well as chemical/cell biology. These include a broad range of cellular, molecular, genetic and “omics’ technologies to better understand, interrogate and manipulate these physiological processes.

Our approaches span single cell, tissue, organoid to whole body physiological performance (using a range of organisms), through to identification of biomarkers in groups of patients with a distinct disease phenotype or response to a therapeutic strategy. Clinical variability is likely to result from an interplay of genetic factors with environmental and lifestyle differences. We are entering the era of ‘precision medicine’ where drug development is moving away from the traditional one-size-fits-all therapeutic approach toward personalised therapies.

Ultimately, linking a molecular pathway or biomarker to a patient group and new sensing techniques will transform our therapeutic approach and the effectiveness of new and emerging medicines.

We have a breadth of expertise in several areas of immune regulation (spanning inflammation, infection as well as respiratory and cardiovascular disease), metabolic diseases/ obesity, neuroscience (neurodegenerative disease, addiction) and cancer. This area is both interdisciplinary and strongly collaborative with clinical, pharmaceutical and biotech partners

Professor Stephen Ward
Professor Jean Van Den Elsen

Medicines Development

This theme provides a centre of excellence for networking, collaboration and innovation in drug design and delivery both at national and international levels with strong emphasis on the needs for patients. The theme has on board dedicated members with strong expertise and pioneering projects in drug design and delivery that facilitates partnership with pharmaceutical industry for medicines development and commercialisation. More specifically, it provides a robust consortium of specialised disciplines in medicinal chemistry, chemical biology, immuno-oncology, metastatic cancer and the microenvironment, skin cell biology and cancer, developmental biology, rare genetic disease, neurodegenerative disorders, regenerative medicine, microbiology, photobiology and pharmaceutics to design, evaluate, formulate and deliver innovative drugs. These drugs include biosensors, biologics, antimicrobials, anti-ageing, anti-cancers and other therapeutic medicines with the potential for global impact across healthcare. The theme also leads innovative projects in medicines design and optimisation of topical (skin and nail) and orally inhaled and nasal drug products as well as prediction of oral and topical drug absorption.

Medicines Development has a distinctive mission to promote collaboration with world’s top researchers in academia and healthcare and to attract ground-breaking program grants and strategic global funding programs in partnership with pharmaceutical industry to tackle the unmet needs of patients and to translate research into development and delivery of innovative drugs for therapies. Presently it is developing cutting-edge educational national and international programs both at master (MRes) and postgraduate (MPhil/PhD) levels. Medicines Development has a strong overarching liaison with other research themes to maximise the CTI’s pivotal role for showcasing research excellence across the University, concentrating one catalysing new interactions between the University Departments as well as across research disciplines within the UK Universities and Centres.

Professor Armando Genazzani of Pharmacology, Università del Piemonte Orientale, Italy
Dr Charareh Pourzand

Advanced bioimaging & medical devices

Gill R. University of Bath

Interfacing life scientists, engineers and healthcare professionals, to develop leading-edge medical technology and devices, and advanced imaging systems.

The aim of the Advanced Bioimaging & Medical Devices theme is to bring together physical scientists and engineers with healthcare professionals and life scientists in the development of leading-edge advanced imaging systems, medical technology and devices . The scope of this theme spans fundamental discovery through to clinical treatment and life-long care. Our vision is to foster creation of novel methods and devices that cover this whole pathway, creating a unique pipeline for therapeutic innovation. Within CTI this theme has three functions: i) creating novel imaging/sensing for discovery & clinical pathways, ii) provide integrated support platforms for the other three themes, iii) translate research findings by creating delivery vehicles and personalised therapies. This Research Theme will be closely collaborating with a newly created Centre for Biosensors Bioelectronics and Biodevices (C3Bio), which brings together a critical mass of researchers working on different aspects of:

- biosensors (sensing elements and techniques)
- bioelectronics (electrophysiology and bioelectronic circuits)
- biodevices (device co-design and integration).

Furthermore, C3Bio closely collaborates with companies such as Abbott Diabetes Care, Oxford Instruments, Airbus, NeuDrive and The Technology Partnership (TTP). In turn this will enhance our interactions with industry to seek for funding and carry out our mobilities.

Members of this theme are encouraged to maintain a focus on the clinical translation and regulatory pathways throughout to ensure their research has a genuine impact on the quality of patient care. The collective regulatory experience gained by CTI members through forming spinouts and partnerships with medical technology sector companies will greatly aid the translation of the Centre’s work.

Professor Richie Gill
Dr James Stone