Introduction

Structural biology brings molecules to life in 3D so that we can unpick how they form, work and interact. It has led to many new insights into how different molecules in the human body keep us healthy, and prompted new disease treatments that modify malfunctioning molecules, such as Tamiflu used to treat influenza, and numerous structure-based drugs that combat HIV.

Molecular structure

Determining a molecule’s structure used to be a long and laborious task, incorporating nuclear magnetic resonance, electron microscopy and X-ray diffraction. But improvements to these techniques have transformed structural biologists’ work, with tasks that once took years now only taking hours to complete. The increase in speed of these technologies has been matched by a huge increase in their availability in the UK, allowing more researchers to probe the structure of individual cells and visualise biomolecules than ever before.

Nowadays, the task of choosing which molecules a structural biologist should interrogate in detail falls to experts in genomics, proteomics, transcriptomics and all the other ‘omics’ technologies – which investigate the roles, relationships and actions of the various types of molecules that make up the cells of an organism. And here too huge strides have been made in recent years, creating an exponentially expanding universe of biological knowledge.

Together, progress in omics technologies and structural biology is allowing many promising molecules to be analysed in exquisite detail. Yet not all, and this is because sample preparation and delivery, the link between omics and structural biology – or the problem and the insight – relies on artisan 20th Century production techniques that are ill-suited to modern biological investigative methods.

Structural Biology theme aims

The Rosalind Franklin Institute’s ‘Structural Biology’ theme aims to remove this bottleneck by revolutionising how molecule samples are produced, stabilised, delivered and transferred.

Not only will this result in an order of magnitude increase in the throughput of samples – transforming the crucial early stages of the drug discovery process – it will also allow ‘just in time’ specimen delivery to instruments, making in situ, real-time molecular research possible, and thereby deepening understanding of how a targeted molecule interacts with its environment.

The deep knowledge and new technology the theme develops will ultimately transform the search for new drugs.

Collaborating for success

Such a quantum leap in capability is beyond the expertise of a single team, discipline or organisation, requiring an all-hands-on-deck approach, with stakeholders based at the Institute’s Harwell-based Hub and 10 university Spokes from across the UK, and others from medicine, academia and industry in a broad range of fields, including biology, chemistry, engineering and computing.

To realise its ambition, the ‘Structural Biology’ theme will also collaborate with the ‘Biological Mass Spectrometry’ theme to advance sample production, given mass spectrometry’s power to separate very pure single molecules, and the ‘Next-Generation Chemistry’ theme to discover and optimise bioactive molecules. Meanwhile, ‘Structural Biology’ and ‘Correlated Imaging’ themes will be tightly integrated in an attempt to realise new types of machines that enhance molecular interrogation by combining the power of X-rays, electrons and photons.

Professor James Naismith

Director

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Theme Leader

Professor James Naismith

Director

Professor Naismith grew up in Hamilton, in the west of Scotland attending local state schools. He graduated from Edinburgh in 1989 with a BSc in Chemistry. As a Carnegie scholar, Professor Naismith obtained a PhD in Structural Biochemistry from Manchester […]

Structural Neurobiology

Errors in neuronal proteins lead to disease. It is important to study structures of these proteins in as native a context as possible that can be examined in a way that can recreate potential disease states, i.e. in genetically modified or patient-isolated systems.

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Chameleon

Chameleon will automate cryo-EM sample preparation giving better, more reliable results than is currently possible. Recent advancements mean that increasingly challenging samples are able to be imaged using cryo-EM, making it possible to determine their structure with atomic resolution.

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C100

This new detector, named C100, is the key to making the cryo electron microscopy method more widely available. The project aims to reduce the amount of energy the detector requires from 200keV and 300keV (the current industry standards) to 100keV, with no loss of quality in resolution.

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Nanobodies

Nanobodies are single domain antibodies derived from camelids, which will enable analysis of complex macromolecules and small proteins. They are a versatile tools which have multiple applications in biomedical sciences due to their small molecular size, high affinity and high stability.

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Heparan Sulfate Biosynthesis

Heparan sulfates (HS) are essential for life. Found around every human cell, these complex polysaccharides mediate a diverse range of structural and signalling interactions between cells and the extracellular matrix.

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Amplus – Large Volume Tomography

High resolution large volume tomography with electron microscopy has the potential to transform our understanding of life, by giving researchers access to the atomic and molecular structure of protein complexes in their biological context – the cell.

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Protein Production UK

Proteins are critical components of all living organisms, and understanding protein structure and function has led to new insights in biosciences and biotechnology, enabling new treatments for a host of diseases, from influenza to HIV and various cancers.

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