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Download Astbury Centre Brochure The Astbury Centre for Structural Molecular Biology ASTBURY CENTRE UNDERSTANDING LIFE IN MOLECULAR DETAIL THE ASTBURY CENTRE CONTENTS Welcome to the Astbury Centre 03 RESEARCH THEMES 04 RESEARCH CAPABILITIES Chemical Biology 08 Structural Biology 10 Biophysics 12 Molecular Interactions in Cells 14 WELCOME TO THE INDUSTRY PARTNERSHIPS 16 FACILITIES 18 ASTBURY CENTRE PhD TRAINING 20 LIFE IN THE ASTBURY CENTRE 21 Welcome to the Astbury Centre for Structural Molecular The Astbury Centre’s pre-eminence Biology. Our Centre was formally constituted in 1999 in Structural Molecular Biology could STAFF PROFILES 22 and uses the latest tools available to understand life unlock the secrets of mankind’s in molecular detail. We hope that you will find much HISTORY 26 of interest in this brochure that describes the full range deadliest diseases. of the Centre’s activities. Our centre today is a lively, buoyant and invigorating CONTACT US 26 The Astbury Centre brings together around 70 academic research arena that allows new research discoveries to be staff and 400 researchers (including PhD students, made. The aims of the Centre are to research mechanisms ASTBURY REPORTS 27 post-doctoral scientists and research fellows) from physics, that underpin health and disease and to develop new tools, the biological and medical sciences and chemistry to facilitate methods and technologies. interdisciplinary approaches to unravel life’s mechanisms. These aims are focussed on distinctive strengths in the The Centre has outstanding expertise and research Centre: the dynamic interactome; communication at the infrastructure with all the major techniques required to carry cell membrane; enabling tools for biological and medical out world-class structural molecular and cellular biology discovery healthcare and host-pathogen interactions. research. Our members address major questions associated with biological mechanisms in areas as diverse as chemical Professor Sheena Radford FMedSci, FRS biology, structural biology, biophysics and molecular Director of the Astbury Centre interactions in cells. www.astbury.leeds.ac.uk www.astbury.leeds.ac.uk 03 RESEARCH THEMES THE ASTBURY CENTRE Our research themes address major impact-oriented challenges by drawing on the full breadth of our interdisciplinary capabilities. In each theme, there is a buoyant portfolio of research involving large numbers of PIs within the Centre that RESEARCH additionally draws on our partnerships with academic, clinical and industrial collaborators. The themes are part of broader remit of Astbury Centre which is to harness interdisciplinary THEMES approaches to understand life in molecular detail. The dynamic interactome Key areas of focus: Enabling tools for biological discovery Key areas of focus: Mission: To understand molecular mechanisms • Intrinsically disordered proteins and intrinsically Mission: To facilitate the development and • Integration of machine learning and technologies to enable across spatial and temporal scales and to uncover disordered regions; application of cutting-edge tools, often inspired discovery of manufacturable biopharmaceuticals; new opportunities for intervention. • Protein-protein interactions and their regulation by by the physical sciences, to enable researchers • “Seeing into Cells” using chemical, biophysical and post-translational modification; to tackle current challenges in biology and bioanalytical approaches to study the mechanism and This theme focuses on understanding and manipulating • The life cycle of proteins; medicine. function of proteins and other macromolecules in cells. biological processes over different time scales, and • Cell signalling networks and interactomes. determining how these molecular mechanisms relate to life. This theme encompasses method- and tool-driven science, Key discoveries made: Approaches exploited include: structural biology, disruptive such as chemical and physical approaches for understanding • Chemical photocrosslinkers for rapid mapping of protein molecular discovery, molecular dynamics, super resolution Key discoveries made: and manipulating biological processes. Our goals are to interactions • Integrated chemical tools and microfluidic technology imaging, chemical tools, single molecule biophysics, develop approaches to drive step-changes in our ability to to map dynamic interactions • Chemical “prosthetics” for restoring protein function biomolecular mass-spectrometry, -omics and cutting edge interrogate biological mechanisms and to facilitate future • Affimers as renewable affinity reagents for studying spectroscopies. • Characterization of functional states of the β-barrel hypothesis-driven life-science research. This includes both biological mechanisms assembly machinery the application and innovative combination of current state-of- Our goals are to drive a step-change in • Understanding of the functional regulation of Aurora the-art tools and the invention and refinement of new tools. • Functionalised quantum dot probes of multivalent protein- ligand interactions our understanding of biological molecular A kinase by protein-protein interactions • A platform for the discovery of diverse functional small • Structural mapping of oligomeric intermediates in amyloid Some approaches currently being developed are: platforms mechanisms via: molecules with novel functions. assembly pathways to discover next-generation small molecule tools, surface • application and innovative combination of state-of-the-art mimics of biological interfaces, advanced microfluidic devices, tools to study biomacromolecule folding, aggregation and • Characterization of allosteric regulation in soft matter tools for biology, computational methods and the interactions in a systems and cellular context mechanosensitive ion channels. development of analytical tools (such as single-molecule • development of methods to manipulate and understand spectroscopy, combined microscopies and structural mass dynamic biomolecular mechanisms. spectrometry). 04 www.astbury.leeds.ac.uk www.astbury.leeds.ac.uk 05 RESEARCH THEMES THE ASTBURY CENTRE Communication at cell membranes Host-Pathogen interactions Key areas of focus: Key areas of focus: Mission: To understand how interactions at cell Mission: To understand the molecular biology • Understanding how signalling at the cell membrane can • Understanding virus lifecycles from infection to release membranes result in cellular responses in health result in disease states of viruses and bacteria that cause disease in using high-resolution structural and imaging approaches. and disease. • Understanding the role of the glycocalyx in transport and humans, animals and plants, and to translate • Leveraging expertise in chemical biology to interrogate signalling across membranes these findings into new tools for prevention, infection and develop novel strategies for anti-infectives. Cell membranes are the centres of communication between • Development of new scaffolds to generate more native-like detection and eradication of these pathogens. the inside and outside cellular worlds. We are working across environments for membrane proteins Key discoveries made: disciplinary boundaries to understand, at the molecular scale, Viruses and bacteria are the cause of significant disease the mechanisms that regulate the reception of signals, their • The single-stranded RNA genomes of many viral Key discoveries made: in humans, animals and plants. For example, bacteria are pathogens are a “self-instruction manual” for the integration and processing, and the formulation of a response. developing resistance to current antibiotics, threatening • Detergent-free isolation of membrane proteins in their lipid production of the infectious virions This is a formidable challenge, but it will provide novel our ability to treat common infectious diseases, resulting environment • Bunyaviruses require cellular potassium to infect cells, opportunities to enhance our understanding of fundamental in prolonged illness, disability, and death. Viral infections a finding that we are harnessing to repurpose clinically- biological processes. Moreover, it will aid in the development • Understanding how extracellular matrix can discriminate are also a cause of global mortality and morbidity, with approved drugs to treat these viral infections of bioactive surfaces, scaffolds and delivery vehicles to cells by their receptor density, and how this pandemic virus being the most significant human disease control and sense cellular fate for applications in regenerative ‘superselectivity’ can improve targeting of cells in risk in the UK, according to the National Risk Register of • Activation of an IL-6 signalling axis drives autocrine STAT3 medicine, targeted drug delivery and diagnostics. biomedical applications. Civil Emergencies (e.g. COVID-19). To reduce the risks of activation, providing an opportunity to use clinically • Re-engineering of peroxisome import pathways to deliver these and other infections, our research uses molecular and approved drugs to treat HPV-mediated cervical cancer cargo to different cellular compartments. cellular techniques, combined with structural and chemical • Oncogenic herpesvirus Kaposi’s sarcoma-associated • Understanding multivalent lectin-carbohydrate recognition approaches, to understand in molecular detail how these herpesvirus (KSHV) sequesters a host cell complex, using functionalised quantum dots. pathogens grow, cause disease and evade treatment. We hTREX, to enhance viral mRNA processing and replication,
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