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OBN BioTuesday at the Rosalind Franklin Institute

The Rosalind Franklin Institute (RFI) recently opened its doors to the OBN community by hosting a showcase and networking evening at their hub building on the Harwell Campus in Oxfordshire. Domainex was represented by Rachel Pearce, Associate Director of Business Development.

The evening was kickstarted with an introduction to the transformative work of the RFI, a new national research institute funded by the Engineering and Physical Sciences Research Council (EPSRC). Research programs selected for the RFI encompass the institute’s values of Adventure, Novelty, Utility and Engagement. These programs would typically be deemed too risky for a single partner, not suitable for typical grant funding, require expertise from multiple collaborators and have a practical end purpose. Jim Naismith, director of the RFI, highlighted two high impact programs which are progressing science through interdisciplinary research and technology development.

Program one: Nanobodies

The first of the programs is in the field of nanobodies — a smaller, simple form of antibody generated by llamas and camels. Nanobodies have been engineered and ‘stitched’ together by a team of researchers to effectively target the SARS-CoV-2 virus that causes Covid-19.

Administration of an engineered nanobody agent to hamsters infected with SARS-CoV-2 showed a marked reduction in disease, with animals losing far less weight and possessing a lower viral load after seven days than those who remained untreated.

Due to the susceptibility of the world population to Covid-19, the virus has millions of opportunities to adapt and evade our human immune system. However, as llamas do not succumb to the virus, their nanobodies present a novel mechanism to combat the virus and could provide a valuable therapeutic for fighting the disease. Nanobodies are also being investigated as a prophylactic agent against SARS-CoV-2. Mice injected with nanobodies within hours of inoculation with the virus had fully recovered with no detectable virus, whereas untreated mice showed damage in the lung by day three.

Of course, this discovery would not have been possible without the participation of Fifi, a llama who is part of the antibody production facility at the University of Reading.

Program two: Structural biology

The second program offered a glimpse into the future of structural biology, seeing the detailed cellular imagery captured by Ruska, a one-of-a-kind electron microscope manufactured in Japan by JEOL. Able to image biological samples at up to a million frames a second, a thousand times faster than the current standard, Ruska can image molecules in motion — ‘filming’ proteins as they fold.

Ruska also enables an examination of the atomic and molecular structure of protein complexes in their native cellular context through high resolution large volume tomography. As with existing cryo-EM, large volume tomography uses frozen samples in a glass-like ‘vitreous’ state. Slices of brain tissue may be scanned with an electron beam and a 3D model can be assembled to give high resolution insight into the structure of a whole cell or collection of cells. These capabilities are being implemented with a focus on studying the mechanisms of bacterial and viral infection and diseases caused by the misfolding of proteins.

The Nucleic Acid Therapy Accelerator (NATA) is a near neighbour on the Harwell campus and also a new UK research initiative, with a mission to accelerate the development of nucleic acid therapeutics. In addition to establishing a new infrastructure within the NATA Hub, the UK Strategic Priorities Fund is injecting £12m into a research challenge scheme to spearhead the formation of international consortia to tackle some of the most pressing challenges to nucleic acid therapy development. Professor Nick Lench, Executive Director at NATA, provided an introduction to the research aims and priorities of the institute and its collaborators.

Nucleic acid therapies have really taken off since 2016, with approval of several drug products offering high impact improvements in human health. However, significant bottlenecks remain to their development. Nucleic acid therapies are amenable to a number of delivery techniques but suffer from inefficient delivery to the endoplasmic reticulum where they act. One of the primary focusses of the current consortia aims to address this limitation though the development of new and improved methods of delivery, chemical modification to improve stability, conjugation to enhance targeted delivery and research to reduce endosomal escape of these therapies. A second significant bottleneck is the manufacturing technologies of nucleic acid therapies. The processes are often not scalable and utilise ecologically unfavourable chemistries. Therefore, a consortium has been awarded with funding to develop enzymatic biocatalysis methods to improve the scalability of manufacture.

An ecosystem for collaborative research

Harwell is a rapidly growing innovation campus, attracting an ever more diverse range of life science organisations. Adrian Hill, HealthTec Cluster Development Manager, provided an update on the new developments and facilities that are establishing a thriving ecosystem for collaborative research.

The networking evening was capped off with the chance to see Ruska and the carefully designed facility that maintains a stable environment, minimising vibration, magnetic fields, acoustic noise and temperature fluctuation.

Thanks to the RFI and OBN for hosting such an inspiring event.

If you have a project that would benefit from structural biology insight and would like to discuss Domainex’s capabilities in X-ray Crystallography and/or CryoEM, then please do get in touch.

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