Scientists are now able to view live molecular interactions as they would occur in the body, thanks to a unique partnership between AstraZeneca, LUMICKS and the University of Cambridge.
The world’s first centre for dynamic single-molecule analysis has been established at the university’s Department of Biochemistry on Tennis Court Road to help accelerate drug discovery. The department now houses a C-Trap optical tweezers-fluorescence microscope – small enough to fit on a desktop, and unspectacular to look at, but capable of extraordinary feats.
Developed by two research groups from the VU University in Amsterdam and brought to market by Netherlands-based LUMICKS, the C-Trap microscope enables scientists to view how disease-causing proteins come into contact with, and interact with, DNA and how drugs affect these processes and block their action.
Dr Geoffrey Holdgate, principal scientist, discovery sciences at AstraZeneca, said: “C-Trap is a unique and powerful tool that could help us unravel precise molecular mechanisms of diseases and the mode of action of lead compounds. “We are excited to be the first pharmaceutical company to use this technology and look forward to working with LUMICKS to validate the potential of single molecule analysis to enhance the drug discovery process.”
Olivier Heyning, CEO of LUMICKS, added: “Establishing the first ever Center of Excellence in Cambridge is an important step in introducing the power of dynamic single-molecule analysis to the biomedical and pharmaceutical research communities. “Our tools enable scientists and pharmacologists to analyse the mechanistic details of processes underlying health and disease, with or without a small molecule drug lead being identified. This paves the way for the design of novel, more efficient strategies for highly-targeted drug discovery, and the selection of higher quality drug leads.
Due to its sensitivity to movement and vibration, the microscope sits on a specially-designed stand. It features a chamber containing a tiny volume of liquid, into which microscopic polymer beads, strands of DNA and the target proteins being studied are floated. Its microscopic tweezers, formed from laser beams, are strong enough to trap pairs of beads which, suspended in the liquid, act as hooks to hold a single DNA molecule. Scientists use a joystick to operate the microscope by manipulating the laser-controlled suspended beads to catch floating strands of DNA, one at a time, and watch as proteins attach onto it.
The proteins being studied are fluorescently labelled, then added to the liquid, making them give off light in a variety of colours so they are visible. The microscope films them as they come into contact with the suspended strand of DNA. Scientists view the fluorescent dots in real time on a computer screen, enabling them to detect the position of the proteins as they attach to the DNA, as well as how those proteins interact with it.
The partners aim to gain a better understanding of how diseases develop, which will help inform drug design.
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