Data Collection to Structure Refinement and Beyond
The mission of the Chan Zuckerberg Imaging Institute (CZII) is to enable deep insights into the architecture of complex biological systems at the molecular level, through the development and application of novel imaging technologies. The initial grand challenge for CZII is to develop technologies and methodologies to image the molecular architecture of the cell to…
Despite treatment and other interventions, an effective prophylactic HIV vaccine is still an essential goal in the control of HIV. Inducing robust and long-lasting antibody responses is one of the main targets of an HIV vaccine. Delivery of HIV Env using nanoparticle (NP) vaccines has been shown to elicit better immunogenicity than soluble HIV Env.…
Electron cryomicroscopy can, in principle, determine the structures of most biological molecules, but is currently limited by access, specimen preparation difficulties and cost. We present a purpose-built instrument operating at 100 keV (instead of the widely-used 300 keV instruments) – including advances in electron optics, detection and processing – that makes structure determination fast and…
Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase that plays a critical role in blood pressure, and fluid and electrolyte homeostasis. ACE can cleave angiotensin I, bradykinin, and many other peptide substrates. Until recently, little was known regarding the specific role of each of the two ACE domains, their 3D structural orientation, dynamics and dimerization. In…
The electron Bio-Imaging Centre (eBIC) at Diamond Light Source offers a unique service to pharma and biotech companies to rapidly advance their discovery and development of lead compounds, biologics, or drug carriers whilst uncovering valuable information regarding biomolecule structure, stability and domain flexibility by using cryo-EM. By offering flexible access to world class cryo-EM facilities,…
Structural biology is essential for the rational design of novel vaccines, drugs, immunotherapeutics, or other biologics. Stabilised HIV-1 envelope antigens have facilitated the discovery of rare broad and potently neutralizing antibodies, and structure-guided stabilisation of coronavirus spikes facilitated the rapid design of SARS-CoV-2 spike vaccines. Similarly, snakebite envenomation, which kills >135,000 people annually, remains a…
The atomic structure of insulin has been known since the late 1960s, but it is only relatively recently that molecular detail has been obtained of the insulin receptor and of the way in which insulin and its receptor interact and effect signal transduction into the cellular interior. These advances have been dependent both on the…
Single-particle cryo-EM, in being able to capture an entire spectrum of states of a biomolecular complex, is uniquely suited for drug discovery as well as development of vaccines. Increasingly the capacity of a biomolecule to “breathe” and change its structure dynamically in the thermal bath is recognized as key in understanding drug efficacy and, more…
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