Congratulations to the Advanced Light Microscopy STP, who recently led a collaboration with five Crick research labs on a successful UKRI MRC Capital Grant submission! The team, led by Kurt Anderson, included the Swanton, Vousden, Briscoe, Priya, and Elosegui-Artola labs, have been awarded £340,344 to purchase a new Slit-Scanning Confocal Microscope for Gentle Live Imaging. Kurt tells us more ...

What is the Slit-Scanning Confocal Microscope and what can it do? 

The NL5+ is useful for imaging thicker specimens such as spheroids, organoids and developmental systems because it hits a sweet-spot of sensitivity, working distance, contrast at depth and compatibility with glass-bottom dishes. Gentle imaging results from the high sensitivity of the slit-scanning approach, which means that samples can be imaged with very low light levels. Intense illumination damages the sample through photo-toxic effects such as free-radical generation. Our preliminary data show that the NL5+ allows sensitive live samples to be imaged deeper and longer than other gentle imaging approaches (e.g. spinning disk or lattice lightsheet). 

How will this improve the Advanced Light Microscopy STP? 

We will have the first NL5+ in the UK, so it will give us an edge on other imaging facilities through new technology. We believe the slit-scanning approach has the potential to become the ‘go-to’ method for imaging samples such as spheroids and organoids. We anticipate that other research labs and facilities will be keen to visit CALM to learn more about this instrument. 

Can you tell us about the application process for the grant? What did you submit and why do you think your application stood out?

I have been on the MRC Equip award panel for a couple of years now, so I had a pretty good idea of what kinds of things the panel likes to fund. Although they like to fund new technology, you must show in detail how the technical features of the equipment you are requesting will enable the experiments needed to answer specific questions. Its not enough to have hand-wavy text saying, “oh, we’re going to do so-and-so...” To be successful, an application must be based on convincing preliminary data, generally from an equipment demo, which shows that the technology will work as described in the experimental system under investigation. In our case, Matt Renshaw organized a fabulous month-long demo and wrangled dozens of samples and users so that we could assemble an extremely strong case for support with outstanding preliminary data comprising publication-quality images (see gallery below). We also had great support from Martin Olsson pulling all of the pieces together.

What advice would you give to other teams hoping to be successful in their bids for similar grant funding? 

Equipment grants are a peculiar type of funding. A good use case should connect all the way from novel equipment features, to the experiments they will enable, to the new information this will provide and how it relates back to the biological question. You also must show that the application team has the expertise to support and use the equipment and analyze the data. Finally, you must have the right number of use cases, described in sufficient detail to be convincing. 

What projects / research will the microscope be used for first? 

Our grant involves five research projects relating to cancer biology (Swanton and Vousden), neuronal development (Briscoe), cardiac development (Priya), and tissue biophysics (Elosegui-Artola), which will benefit from the use of this technology. These projects are united by the need for gentle live imaging, especially of spheroids, organoids, and developing systems. Beyond the work described here we anticipate the utility of the NL5+ for many Crick research projects requiring gentle 3D imaging of thicker specimens. 

(Posted on Cricknet by Alex Peake, 18/07/24)