Industry
Industry
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 four key industry-facing themes: targeted molecular delivery; predicting and preventing protein aggregation; emerging target classes; membrane proteins in health and disease.
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. Emerging target classes
We are focusing on several emerging target classes in drug discovery, exploring their potential to address previously unmet medical needs and open new avenues for therapeutic development. Major efforts are to make use of event-driven pharmacology and proximity-inducing concepts.
Examples of research at Leeds include:
- Protein Degradation: Developing small molecules and other agents that can selectively degrade disease-causing proteins, including those considered "undruggable".
- Neurodegenerative Disease Targets: Identifying new targets for neurodegenerative diseases like Alzheimer's and Parkinson's, with a focus on misfolded proteins and neuroinflammation.
- Intrinsically disordered regions and proteins (IDRs/IDPs): Developing new strategies and molecules to selectively target IDRs and IDPs.
- Immune Checkpoints: Developing therapies that target immune checkpoints to enhance the body's immune response against cancer and other diseases.
Theme Lead – Professor Elton Zeqiraj
4. Membrane proteins in health and disease
Membrane proteins are the target of over 50% of therapeutics and are important for treating a breadth of diseases from cancer to diabetes.
We have both extensive expertise in membrane protein structure and function studies, and world class instrumentation.
This includes cryo-electron microscopy, mass spectrometry, atomic force microscopy, molecular dynamic simulations, NMR and a breadth of analytical techniques. Moreover, Leeds has a depth of expertise in studying membrane composition and developing new scaffolds to house membrane proteins, including hybrid vesicles and polymers.
Examples of research at Leeds include:
- Ion channels: We have developed a range of small molecules against ion channels involved in a range of disease states such as vascular disease, epilepsy, and cancer.
- Receptor Tyrosine Kinases: Cell signalling is a key process and errors are linked to diseases such as cancer and diabetes with work ongoing on several family members including FGFR, EGFR, and VEGFR.
- New technologies: We have been developing new scaffolds to better stabilise membrane proteins for structural and biophysical analysis including polymers and hybrid vesicles.
Theme Lead – Dr Stephen Muench
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