As a mechanism to improve innovation, partnerships between academia and companies are playing an increasingly important role.
“In working with the University of Leeds on this project, we gain access to expertise from many disciplines which is being focussed on the prediction and prevention of protein aggregation – this is one of the key obstacles facing the development of biotherapeutics today” - Andrew Buchanan, Principal Scientist, AstraZeneca
Despite huge investment and changes in practices over the years, the rate of drug discovery has not increased and the cost of bringing effective drugs to market remains very high. We have strong links to a wide range of companies in the Life Sciences sector – this ensures that our research is highly relevant to industry, and has the strongest potential for translation.
Industry Advisory Board
One mechanism through which industry links are developed is the Astbury Centre Industry Advisory Board. Our Industry Advisory Board comprises representatives from the pharmaceutical sector and relevant SMEs, and also provides links to key national initiatives.
Challenge-led research priorities
By working closely with our Industry Advisory Board, we are able to match our distinctive capabilities to market need and maximise the opportunities for translation of our research. We have five key industry-facing themes: inhibiting protein-protein interactions; targeted molecular delivery; predicting and preventing biopharmaceutical aggregation; ion channels research; and translational drug discovery.
1. Targeted molecular delivery
We are developing multiple systems that are capable of delivering reagents with control of pharmacokinetics and biodistribution. This allows the delivery of reagents including RNAi to large proteins for applications in therapeutics, imaging and/or diagnostics.
Getting a reagent or therapeutic agent to the desired site can be a challenge, especially for larger biotherapeutic products and hydrophobic drugs. Delivery systems which can target the site of disease have the potential to greatly improve the outcome of a therapy.
Examples of research at Leeds include: synthetic polymers, gold nanoparticles, nucleic acids, aptamers, microbubbles, multicompartmental nano structures, bacterial toxins and virus-like particles.
Theme Lead – Professor Bruce Turnbull
2. Predicting and preventing protein aggregation
We integrate experimental and computational approaches to understand, predict and control the properties of biological molecules. Our infrastructure and expertise in biophysical and structural methods allows us to study molecular mechanisms of the aggregation process.
The rise in the development and approval of biopharmaceuticals has led to a raft of new challenges that require solutions. For example, preventing aggregation during the production of biopharmaceuticals is a major challenge for the sector.
Examples of research at Leeds include: subjecting biopharmaceuticals to extensional flow to test the robustness of these proteins to the stresses of production; and an in vivo directed evolution method to identify and/or re-engineer manufacturable biopharmaceuticals early in development.
Theme Lead – Prof David Brockwell
3. Protein-protein interactions
Protein-protein interactions (PPIs) regulate large numbers of processes within the body and underpin the majority of biological activity. However, the molecular basis of PPIs, and how they orchestrate biological function is poorly understood. PPI inhibitors have the potential to modulate disease progression, and therefore the ability to design such molecules could open many opportunities for therapeutic intervention. A current EPSRC programme grant PoPPI (link to : https://poppi.website/) is geared towards transforming early-stage PPI inhibitor discovery and focusses on development of computational tools to classify PPI recognition motifs, together with generic scaffolds that may be readily decorated to selectively target specific PPIs
Examples of ongoing research at Leeds include: development and commercialization of “tag transfer” reagents for mapping dynamic protein-protein interactions, and the development of experimentally validated methods for the prediction of hotspot residues at protein-protein interfaces.
Theme Lead – Professor Andy Wilson
4. Ion channels research
Research focussing on understanding normal human functioning and the mechanisms of disease is applied to numerous ion channel types with impact on multiple diseases.
Leeds’s pre-eminence in ion-channel research has led to a depth of expertise enabling the generation of established ion channel reagents, but also the development of emerging, novel channels targets. Ion channels are a major target for drug development by the pharmaceutical industry in their search for effective therapies in a plethora of diseases.
Examples of research at Leeds includes: Ion channels in vascular disease, structure and cell biology, function and molecular mechanisms, sensory neurone ion channels and the modulation of pain and epilepsy, voltage gated ion channels and Alzheimer’s disease and host cell ion channel function as a novel target during virus infection.
Theme Lead – Dr Stephen Muench
5. Translational drug discovery
Novel small molecules and biotherapeutics have been identified targeting a range of protein classes. Examples of research at Leeds includes: virology research to understand the molecular basis of replication and pathogenesis leading to structure based drug design of novel antiviral therapeutics; oncology research focused towards the identification of agents for use against novel targets of applied and clinical relevance; and cardiovascular research that uses engineering and other fundamental disciplines to develop innovative approaches for cardiovascular diagnosis and protection.
Research developed within the Centre has contributed to a number of successful spin-out companies, including LUNAC Therapeutics and CalTIC, as well as the commercialisation of technologies, such as Affimers, as a versatile class of non-antibody binding proteins.
Theme Lead – Dr Richard Foster
Examples of research of direct relevance to industry
- A versatile cholera toxin conjugate for neuronal targeting and tracing
- Protein-conjugated microbubbles for the selective targeting of aureusbiofilms
- A NIR-II-emitting gold nanocluster-based drug delivery system for smartphone-triggered photodynamic theranostics with rapid body clearance
- Human TRPC5 structures reveal interaction of a xanthine-based TRPC1/4/5 inhibitor with a conserved lipid binding site