ELF project member spotlight: Jason Swedlow, University of Dundee

04 November 2020

Phenotypic screening is a powerful approach to identifying novel chemical starting points for drug discovery, offering the potential to uncover new drug targets and pathways underpinning disease-related biology. High Content Screening (HCS) is one of the phenotypic screening approaches offered by the European Lead Factory (ELF). To find out more about HCS and all it entails, we spoke to Professor Jason Swedlow, head of the National Phenotypic Screening Centre (NPSC) at the University of Dundee – one of ELF’s academic partners.

Can you tell us a bit about your background and what your role is within the European Lead Factory?

I’m a cell biologist and I specialise in using imaging to study the mechanisms and processes of cell division and growth. I have 20 years of experience in handling the imaging data associated with image-based assays and I lead a large project called the Open Microscopy Environment that builds the software used for handling these datasets. One of my roles at the University of Dundee is that of academic lead for the NPSC. Within ELF, I represent the NPSC and am in charge of the HCS activities for the programme.  

Can you explain what HCS entails and what it adds to the European Lead Factory?

The NPSC is the HCS facility for ELF. We provide the capabilities, assay infrastructure, expertise, data handling, and analysis for HCS assays within the programme. To date, most of ELF’s activities have been more focused on High Throughput Screening (HTS). We have come on board to supplement that effort with phenotypic assays and image-based assays using HCS. While HTS provides an enormous amount of information and value in looking at specific targets, HCS is used to analyse the effects of compounds and gene-based perturbations, looking at how those compounds affect cells or various biological models of cells and tissues. The general approach involves setting up some kind of system that’s based on growing cells, either in a 2-D model layer (on a flat surface) or a larger 3-D structure that mimics the properties of tissues. We then use various imaging assays to measure the effects of compounds in a way that reflects their activities in biological mechanisms for targeting.

A subset of the ELF compound collection (50,000 compounds) has been created for the NPSC to screen, how far into this process are you?

We are now in the process of sourcing screens for assays and identifying candidates for screening within ELF. This involves a lot of engagement with the community and has been a very interesting process so far. At the NPSC we have a wide variety of collaborators who are developing assays and are interested in running them against publicly available compounds for discovery and mechanistic insight. As we’re developing these assays, we have the opportunity to feed these into the ELF programme. We’re now in the middle of that process of feeding these assays in and having them evaluated by ELF.

In addition to leading the High Content Screening for ELF, you are also part of the ELF Review & Selection committee. How do you experience your role in this committee?

This has been a great learning experience for me. I really enjoy being part of the review panel as I get to work with incredible scientists from a very broad community, in particular across the community of industrial research and large biotech and pharma in Europe. It’s interesting to gain insight into how they think about the construction and execution of assays. Some of the work is extremely technical, but an awful lot is strategic with a focus on how different types of assays and targets fit into the current priorities of the European pharmaceutical community. It’s always educational to be part of these conversations. My role on the panel is to represent the phenotypic side and the challenges of running these larger phenotypic screens. We don’t want to just admit any assay that is submitted; running these assays takes a significant amount of work, materials and time, so it’s quite an investment. One of my roles is to work through the requirements for the HCS assays, ensuring they are strict enough to guarantee high quality assays and hits. We also try to identify those assays that are innovative and exciting enough to make a real impact.

What interests you most about the European Lead Factory and what do you hope to add to the project?

In my experience as a scientist, the best outcomes derive from interactions (and sometimes collisions) with people from different fields. What I really enjoy is the opportunity to talk through scientific strategies, choices and priorities with colleagues from different sectors. It’s a learning process, but it’s also a valuable exchange of ideas with people outside of one’s normal day to day business. I believe quite strongly in the goal of connecting innovative science with the incredible chemical capabilities and libraries that are available in the European pharmaceutical sector. It’s through these connections that the most valuable science happens. This is perhaps the most important aspect of ELF for me – the fact that it bridges gaps between different players to drive innovative science. It provides fantastic opportunities for impacting biomedical science in a meaningful way.

What tips would you give to potential applicants planning to submit a (High Content Screening) proposal to the European Lead Factory?

What I strongly suggest is to talk to us. ELF is a well-established programme and there’s a whole process by which assays are brought in and evaluated. Understanding what that process is, what is being sought, and what the priorities are is extremely important. While it’s definitely possible to gather all the information one needs from the ELF website, I strongly urge scientists or institutions looking to submit applications to get in touch directly with the ELF programme office to talk through what they have, what they want to do, and what we can provide. It’s really important to have these conversations so that everybody understands what the proposal is and what the opportunities are.

To find out more about the National Phenotypic Screening Centre, follow this link. If you’re interested in submitting a screening proposal to ELF, get in touch with the programme office via email or join our weekly online Q&A hour where a member of the programme office will be available to answer questions about ELF and the proposal submission process. The next deadline to apply is Friday, 22 January 2021.