5 Ways Cell-Based Screening Is Revolutionising Drug Discovery

When it comes to drug discovery, understanding cell biology at all levels can accelerate development of new treatments. Whether exploring a disease mechanism or investigating new molecular therapeutics, cell-based assays are crucial to support and innovate at all stages of the drug discovery pipeline. To keep advancing healthcare through new treatments for disease, it is imperative that cell models are state-of-the-art, facilitating the translation of therapeutic effects to human physiology.

Cell reagents, assay formats, and readout optimisation can all contribute to the development of more translatable models, thereby improving success rates in drug discovery. However, restrictions in cell availability and assay costs are holding back broader implementation of cell assays with improved translatability. So, how can we adapt cell profiling efforts to improve cell assay profiling and tackle emerging drug modalities?

In this blog, we discuss five cutting-edge advances and applications of cell-based screening covered at the fourth ELRIG Advances in Cell Based Screening in Drug Discovery event, where speakers will be highlighting challenges and major breakthroughs in these areas.

Learn all about the latest developments and opportunities in cell assay profiling by registering for the free event, held in person on May 10-12 2022 at the AstraZeneca R&D site in Gothenburg, Sweden.

1. Enabling advanced cell models in profiling

Cell models have enabled researchers to develop new treatments for many conditions, including HIV and polio. While these treatments are effective, translational challenges from 2D to 3D cell models hinder understanding of biological systems and drug treatments. To better mimic the biological system being investigated and to ultimately advance and produce new treatment, improvements to these models must be made. Janine Scholefield, keynote speaker, discussed the importance of defining your research question to ensure the model best fits the question being answered in our previous blog. Approaching your problem in a different way — particularly taking into consideration the effects of genetic background — is a key step Scholefield emphasised researchers can take to influence the success of your project from an earlier stage of development.

Unfortunately, even the most physiologically relevant assay can only provide a limited amount of information on its own. One approach you can take that allows you to gain more data from your cellular models is using new technologies to increase the throughput of your study. In her presentation, Lorna Sucking, GlaxoSmithKline, explains the roles miniaturisation and automation can play in moving cell-based assays to high-throughput analysis. By maximising the amount of disease relevant data obtained through automated screens, cell-based assays can play an ever-expanding role in developing new treatments.

2. A complete temporal and special understanding of cellular responses

To improve the quality of data from cell-based assays, a true understanding of cellular responses and mechanisms can provide essential information and better highlight where research time should be invested. For example, when predicting efficacy of drugs in humans, inhibitor affinity is currently the most commonly used parameter. While this is a useful tool, investigating different parameters can shine a new light on problems and provide innovative solutions. At the event, Benedict-Tilman Berger, CELLinib GmbH addresses how often-neglected binding kinetics can play a highly important role in understanding kinase inhibitor efficacy.

Further experimental opportunities are available to researchers to better investigate the mechanism-of-action of bioactive approaches, including chemoproteomics. Keynote speaker Marcus Bantscheff addresses how characterising the mode of action (MOA) of drugs via this method this can contribute to better target engagement and selectivity. The mechanistic findings obtained from chemoproteomics studies are crucial to support development of more effective drugs by having a better understanding of how treatments behave in the body.

3. Cell profiling support for therapeutic OLIGO discovery

For supporting development of new treatments, cell-based assay technology must also keep up with new types of treatments in drug discovery. One such emerging treatment, use of therapeutic oligonucleotides (OLIGO), works by modulating gene expression by many different processes, including splicing modulation and programmed gene editing. It is therefore critical that cell profiling is designed in a way to support research into these bioengineering approaches.

Molly Stevens, Imperial College London, focuses on addressing healthcare challenges through balancing fundamental science investigation with technology development. Her group reports a range of versatile technologies that can transform biomedical innovations. While her talk focuses on many breakthroughs in regenerative medicine, Stevens highlights how spatially arranged biochemical cues, such as acoustic stimulation, can produce engineered muscle with bundles of aligned fibres.

Extracellular vesicles (EVs) represent another highly important biotherapeutic approach. Speaking at the event, Samir EL Andaloussi, Karolinska Institutet, Sweden, understands the special role that protein therapeutics can play for treating genetic diseases. Now focusing on engineered EVs for biomedical applications, EL Andaloussi’s talk covers how cellular engineering facilitates successful application of EVs for drug delivery. Only advances in cell-based profiling can enable ground-breaking technologies such as these to become a medical reality.

4. High throughput protein MS in cellular profiling

Due to advances in both technology and our understanding, high-throughput approaches are massively changing the face of research. As well as Suckling’s miniaturisation work for finding more disease relevant data for drug discovery, high-throughput research can be highly useful for providing insights via protein mass spectrometry (MS).

One of the most revolutionary ways that protein MS is being used to advance healthcare is through high-throughput proteomics research, providing insight that simply can’t be gained from other approaches. Characterising the entire protein complement of cell lines, tissues, or organisms, provides a more integrated view of biology by studying all the proteins of a cell. Proteomics can even be used to analyse human blood and blood-derived products, such as plasma. A wealth of biological information can be obtained from plasma, and new and improved methods to facilitate plasma proteomic profiling are of high interest.

Philipp Geyer, co-founder and Chief Scientific Officer (CSO) of OmicEra Diagnostics GmbH, understands the promise of plasma proteomics for discovering novel biomarkers. In his talk, Geyer provides insight into the cornerstones of high-throughput proteomics — lab automation and a robust MS system — enabling analysis of thousands of plasma samples. Through this knowledge, researchers can identify new biomarkers across diseases, providing true understanding of human health and disease stages.

5. Using biology for fingerprinting compounds

Even before high-throughput approaches are considered, the diversity of information gained

from proteomics over recent years has huge implications for improving healthcare. As an example, when it comes to understanding how drug-like molecules interact with the body, chemical biology tools are indispensable. For systems such as protein-drug interactions, investigating them from a proteomics-based perspective provides valuable insight into drug discovery.

Ilaria Piazza, Max Delbrück Center for Molecular Medicine, Germany, has dedicated her research to the application of chemoproteomic methods in complex biological systems. At the event, Piazza’s talk provides insight on her group’s creative proteomic technique, limited proteolysis (LiP)-MS. This tool can be used to discover novel protein-drug interactions in microbial and human organisms, providing detailed insight into global structural changes in the proteome.

Discovering a better future together

Whether supporting development of new treatments, enabling high-throughput research, or allowing better understanding cellular responses and mechanisms, cell-based assays are fundamental for the advancement of drug discovery and broader application of treatments. But how do we ensure that innovative advances such as these are being used and shared to benefit healthcare? We believe that those in the field —in academia, industry, the vendor community, or elsewhere — need to come together in an open environment to network and discuss the latest advancements and applications in cell-based screening.

ELRIG Advances in Cell Based Screening in Drug Discovery 2022 is a free-to-attend event focused on improving and advancing cell assay profiling. For three days, from May 10-12, researchers across academia and industry are invited to network in-person and share their viewpoints and knowledge to improve success rates in drug discovery.

Be inspired and register to attend this exciting event at AstraZeneca, Gothenburg today.

Register for Cell Based Screening in Drug Discovery 2022 Here