The NCMM Chemical Biology Platform
Dr. Johannes Landskron describes how the platform supports researchers with drug discovery and precision medicine projects
Dr Johannes Landskron in the lab. Photo: Øyvind Eide.
Dr Johannes Landskron has been head of the Chemical Biology Platform at NCMM since 2017. The core facility is based at NCMM but offers services to the whole of UiO and researchers at Oslo University Hospital (OUH) and further afield. Here, he describes how the platform supports researchers.
How does the Chemical Biology Platform support researchers?
My team and I help researchers who want to explore potential new drug targets, search for tool compounds or those who are working on precision medicine projects. We offer services around high throughput screening (HTS), meaning we use automated equipment to rapidly test large numbers of chemical compounds for a specific biological or biochemical target.
Performing an HTS is the initial step of any drug discovery project for new drug targets or for the development of tool compounds that are used for research purposes. In both cases, thousands of compounds are screened to identify so-called hit compounds that show the desired effect in a biological or biochemical system. Hits are then further validated and characterized and can be taken forward to medicinal chemistry to develop lead compounds. For these purposes, we have a collection of approx. 70,000 compounds that contain about 10,000 known and well characterized bio-actives. These bio-actives again contain more than 3,500 approved drugs that are used for drug repurposing, in particular for precision medicine projects at Oslo University Hospital. Clinically relevant drugs and novel drug combinations are tested on cancer patient-derived biopsies to find optimal treatment conditions for individual patients. The screening data generated can then be combined with other ‘omics data, for example genomics or proteomics data that give insight into the molecular landscape of a particular tumour. Combining all of this information would then allow you to determine which treatment could work best for a tumour or disease.
We’re also the managing partner of the national Research Infrastructure NOR-Openscreen, with additional nodes at the University of Tromsø, University of Bergen and SINTEF in Trondheim. The National RI is a member of the European Research Infrastructure Consortium (ERIC) EU-Openscreen (which currently has nine participating countries) and the Nordic Chemical Biology Network. This helps us to connect researchers to other facilities and experts outside of our specialty areas. The communities offer access to large libraries e.g. the 100 K compound library from the ERIC, but also to smaller libraries that we share with Denmark, Finland, and Sweden. We also serve as the entry point to this broad infrastructure network for our users. We can help put researchers in touch with experts abroad from other fields that are not available in Norway.
Do you work with researchers in a clinical setting?
Many of our users are from OUS, however, these projects are purely scientific research, since we’re not accredited for diagnostics. We are participating in several proof of concept studies that aim to be translated into clinical procedures. The only occasion we could get involved with projects in the clinic is when patients have reached the endpoint of standard treatment. In such situations, the clinician is free to prescribe whatever approved drug with patient consent. Data created with the support of our facility could, in such a setting, help to guide clinical decisions.
Our robotics capabilities can also be applied in other situations. For example, we did examine the possibility of contributing to the preparation of samples for COVID-19 PCR tests. We didn’t go ahead with this, but it would have been an interesting and timely use of our facility.
How do you work with Oslo’s hospitals?
Our main link is to Radium Hospital. A lot of the basic research here is very disease-focused, investigating the underlying molecular mechanisms of diseases. If a researcher identifies a novel molecular player, this often can serve as a new drug target. The next logical step for them is to develop a specific drug. Rather than conducting a large and quite random screen, we have a collection of around 3,500 FDA-approved drugs in our library and these can be tested for repurposing exploring so far unknown off-target effects. Once they are pre-approved for one indication, it’s much easier to get them into clinical trials for a new approval.
We are also formally connected to the Department of Core Facilities, led by Prof. Leonardo Meza-Zepeda, via a Helse Sør-Øst-funded bioinformatician position which is held by Maria Angeles Jimenez Sigstad. The position is formally located at Radium, but tightly connected to our facility at NCMM. This creates an ‘outpost’ at the hospital and helps us to better connect to the Dept. of Core Facilities and our hospital users.
How is the bioinformatician position shared across OUH and NCMM?
As well as having office space at both facilities, our shared bioinformatician (Maria) will work with data analysis and software development for both OUH and NCMM users. Maria will also work with the maintenance of our compound and assay data databases, making sure they fulfil the international standards and that data is FAIR (Findable, Accessible, Interoperable and Reusable). This will bring it in line with the European consortium, EU-Openscreen, that we are involved in. Having a dedicated bioinformatician means that the rest of the team can focus more on their core tasks and also that we can further develop our bioinformatics services.
What opportunities will the move into the Life Science Building and forming a joint facility between UiO and OUH bring for you and your team, and the services you can offer?
The planned move will bring huge benefits for us as we will automatically become more closely connected to the other UiO core facilities. We already collaborate with some of them, but being housed under one roof means that we can offer a one-stop-shop for many researchers’ needs. It also means we can share expertise when needed and purchase shared instruments, which has previously been impossible due to all our different locations.
Case study: The Jorrit Enseink Group, Oslo University Hospital
We have several long-term projects with research groups from the hospital, working on various approaches for personalized medicine. In addition, we ran several “classical” chemical biology high throughput screens addressing specific cellular or molecular targets. A good example is a screen with the research group of Jorrit Enserink targeting cancer cells specifically that carry the “Philadelphia Chromosome”, a chromosomal translocation common to chronic myeloid leukemia and acute lymphoid leukemia. We could identify a promising lead structure that has been taken forward and is currently tested in animal models. (https://doi.org/10.1074/jbc.RA120.015285, PMID: 33303632).
Learn more about the platform here: https://www.med.uio.no/english/research/core-facilities/chemical-biology-screening/
For further questions, you can contact Johannes at: firstname.lastname@example.org