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Sussex Crystallization Platform for Bioscience discovery

Lead Research Organisation: UNIVERSITY OF SUSSEX
Department Name: School of Life Sciences

Abstract

We are seeking funding to purchase new state-of-the-art crystallization equipment for the School of Life Science's crystallisation facility to enable us to visualise and study the way in which large molecular machines control the replication, survival and growth of human cells and how the protein complexes produced by microbes exploit and disrupt human cell systems. Central to this work is the ability to capture these proteins and protein complexes in solid crystal form to allow us to take a 'snapshop' using X-rays to determine their three-dimensional shape and detailed atomic structure and how this is altered in different conditions.

Financial support is sought for the purchase of a state-of-the-art crystallisation platform to enable us to do this faster, more efficiently and more effectively. The platform platform has integrated software and comprises a crystallization robot, an advanced large capacity automated crystal imaging system and a next-generation liquid handler for crystallization screen building. The equipment will be housed in the crystallization facility at Sussex which has been highly successful in advancing our bioscience discovery research portfolio on the structure and function of macromolecular assemblies; the large number of outputs generated from this research has led to Sussex being internationally recognised as a centre of excellence for structural biology. Building on these discoveries, the facility has also enabled the growth of our translational research activities with the Sussex Drug Discovery Centre and resulted in a rapid expansion of the number of structure-led compound and drug discovery projects initiated across the School.

This new equipment will enable us to move at pace with our programmes of bioscience projects and to generate higher quality data and experimental outcomes.

Technical Summary

We are seeking funding to purchase new state-of-the-art crystallization equipment for the Sussex University crystallisation facility. Financial support is sought for the purchase of a platform with integrated software comprising a crystallization robot with lipidic cubic phase (LCP) capability, an advanced large capacity automated crystal imaging system and a next-generation liquid handler (with microfluidic technology) for screen building. The crystallization facility at Sussex underpins our highly successful bioscience discovery research portfolio on the structure and function of macromolecular assemblies; the large number of outputs generated from this research has led to Sussex being internationally recognized as a centre of excellence for structural biology. There is now a pressing need for us to build on this success by accelerating and expanding our structural biology capability to push forward our bioscience research through the purchase of equipment with increased capacity, reliability, efficiency and functionality.

The projects enabled by the new platform span our areas of strength in Bioscience discovery in the BBSRC priority areas 'Understanding the Rules of Life' and 'Bioscience for an Integrated Understanding of Health'. Our overall objective is to obtain key mechanistic insights into the structure and function of the proteins and protein complexes that regulate fundamental cellular processes and to use these insights to improve human health across the life course through both our advanced knowledge of cell regulation and through the development of new interventions. Our projects aim to address key questions across 5 main themes:
1. Transcriptional regulation and epigenetics
2. Protein kinase regulation and function in health and disease
3. DNA replication and DNA damage and repair pathways
4. Microbiology
5. Ligand interactions and structure-led small molecule discovery

Publications

10 25 50
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El Omari K (2024) Utilizing anomalous signals for element identification in macromolecular crystallography. in Acta crystallographica. Section D, Structural biology

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Bainbridge L (2023) Primase-polymerases: how to make a primer from scratch in Bioscience Reports

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Zabrady K (2023) Mechanism of primer synthesis by Primase-Polymerases. in Current opinion in structural biology

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Bainbridge LJ (2023) Coordination of Primer Initiation Within the Catalytic Domain of Human PrimPol. in Journal of molecular biology

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Zabrady M (2023) Reverse transcriptases prime DNA synthesis in Nucleic Acids Research

 
Description Establishment of High-Throughput Capacity: The primary achievement was the successful procurement and integration of the state-of-the-art crystallization robot and automated imaging system. This has increased our screening capacity by 80%, allowing for the exploration of a vastly larger chemical space for protein crystallization.

Advancement in LCP Capability: The Lipidic Cubic Phase (LCP) functionality has specifically enabled the facility to tackle "hard-to-crystallize" membrane proteins, which are critical targets in our Protein Kinase and Ligand Interaction themes.

Precision and Efficiency: The next-generation liquid handler with microfluidic technology has reduced sample consumption by 50%, enabling the study of rare or difficult-to-purify macromolecular assemblies.

Collaborative Impact: The platform has served as a central hub for the Sussex structural biology community, supporting over 10 PIs and their groups across the 5 core themes, notably in DNA Damage and Repair
Exploitation Route The insights gained from the Ligand Interaction theme are being taken forward by the Sussex Drug Discovery Centre (SDDC) to develop new small-molecule inhibitors for cancer

Preliminary data generated by this platform has already contributed to 3 new successful grant applications, ensuring the long-term sustainability of the research.

Findings will be shared via the Protein Data Bank (PDB) and peer-reviewed publications, making the structural data available to the global bioscience community for further functional studies.

We are exploring potential collaborations with industrial partners in the biotech sector to utilize the platform's high-throughput capabilities for fragment-based drug screening.
Sectors Pharmaceuticals and Medical Biotechnology

 
Description The Sussex Crystallization Platform has transformed the University's structural biology capabilities from a conventional facility into a high-throughput engine for drug discovery and mechanistic bioscience. By integrating state-of-the-art robotics and microfluidic liquid handling, the award successfully eliminated the primary technical bottleneck-high sample consumption and manual screening-allowing researchers to tackle complex "low-biomass" targets that were previously inaccessible. The most significant impact beyond academia has been the de-risking of early-stage drug discovery. By providing high-resolution structural "blueprints" for protein kinases and DNA repair enzymes, the platform has enabled more precise hit-to-lead optimization, directly contributing to the structural data used in projects funded by medical charities to understand disease pathways in oncology. Within the research community, the award has nucleated a center of excellence that bridges fundamental research with applied clinical insights. It has served as a vital training ground for the next generation of UK scientists, equipping PhD and postdoctoral researchers with expertise in automated crystallization and integrated software workflows. By accelerating the transition from protein purification to atomic structure, the platform has ensured that Sussex remains at the forefront of global structural biology, providing the foundational knowledge necessary to improve human health across the life course.
First Year Of Impact 2023
Sector Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description A NEW WOLFSON CENTRE FOR MOLECULAR STRUCTURE
Amount £500,000 (GBP)
Funding ID PR/oys/jw/md/23665 
Organisation The Wolfson Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2023 
End 04/2026
 
Description Developing drugs for the treatment of Epstein-Barr virus positive blood cancers
Amount £279,323 (GBP)
Funding ID 23025 
Organisation Blood Cancer UK 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2024 
End 07/2026
 
Description LMO4 as a drug target in mast cell malignancies
Amount £201,659 (GBP)
Funding ID Blood Cancer Uk (OMAZE) n. 23024 
Organisation Blood Cancer UK 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2024 
End 09/2025
 
Title The human RIF1-Long isoform interacts with BRCA1 to promote recombinational fork repair under DNA replication stress 
Description Raw data associated with the manuscript 'The human RIF1-Long isoform interacts with BRCA1 to promote recombinational fork repair under DNA replication stress'. This excel file contains source data underlying the graphs and uncropped gel/blot images presented in the figures. 
Type Of Material Database/Collection of data 
Year Produced 2025 
Provided To Others? Yes  
Impact Dataset contribute to the mechanistic model 
URL https://springernature.figshare.com/articles/dataset/The_human_RIF1-Long_isoform_interacts_with_BRCA...