State of the art direct electron detection at the Astbury Biostructure Laboratory

The Astbury Biostructure Laboratory, was established in 2015 with University of Leeds investment, and a Wellcome multi-user equipment award, allowing us to install two Titan Krios microscopes (2016).

In just three years, we have established an international reputation for excellence in cryoEM, and a buoyant user base that means our facility is already operating at capacity.

We request funds to upgrade our microscopes, aiming to increase data acquisition rates, whilst improving data quality, allowing us to shorten session lengths, increase sample throughput, and introduce new methodologies. Upgrades will include: 1. A ThermoFisher Falcon-4EC camera on Krios#1 2. A Gatan Bioquantum K3 on Krios#2 3.

Aberration-Free/Fringe Free Imaging Systems (both microscopes) 4. EPU-D software for electron diffraction (Krios#1) 5. Whole-system maintenance contract extensions to 5-years from installation.

We anticipate a 5-8x improvement in data acquisition, empowering users to drive more challenging biological and biomedical discovery.

We will be able to determine new high-resolution structures and integrate them into their cellular/tissue context, helping us to understand the molecular basis of diseases such as infections, cardiovascular disease, degeneration and cancer.

We request £1m from Wellcome, with a University capital contribution of £325k, plus salary costs, Giving a total project cost of ~£2.13m.