REFRAMING CELLULAR MODELLING: A MORE GLOBAL APPROACH
Advances in cell biology have revolutionised how we approach healthcare. New techniques including stem cell research, CRISPR, and gene therapy allow us to investigate treatments for conditions such as cystic fibrosis – and researchers are only just scratching the surface. However, cell biology is notoriously challenging, due to many complicating factors affecting cell growth and experiment reproducibility.
Dr Janine Scholefield, Research Group Leader at the Council for Scientific and Industrial Research, South Africa, specialises in developing new cell models that better mimic physiology, particularly in relation to genetic backgrounds. In this blog, Janine discusses challenges in cell profiling, and how looking at problems in a more global way earlier in the process can improve the quality of healthcare research.
Hear more from Dr Scholefield in her Keynote and take the opportunity to learn all about the latest developments and opportunities in cell assay profiling by registering for the fourth ELRIG Advances in Cell Based Screening in Drug Discovery event, held on May 10-12 2022 at the AstraZeneca R&D site in Gothenburg, Sweden.
The humble cell
Many problems can be solved with cell biology that simply can’t be tackled by any other approaches. For example, models made from the most commonly used cell line – HeLa cells – have been instrumental to aid understanding in research areas from HIV to polio vaccines. However, there are many challenges with cell assays, in particular, how to effectively translate them into human physiology.
One of the main challenges in developing more relevant models is the translation from a 2D to a 3D system. Normally, most research is conducted using a 2D cell model, as these are easier for researchers to handle and manipulate. However, they aren’t perfect physiological mimics. In vivo tissue consists of a complex 3D architecture within an extracellular matrix, which can’t be accurately replicated within a 2D system. Therefore, it is important to develop new models that better mimic the system being investigated.
But how do we improve our models? Janine believes that while models need to be more physiologically relevant, they don’t have to be perfect. “What is it you’re trying to answer?” she asked. “To mimic a specific aspect of liver function, you don’t need to make 3D liver organoids that are exact functions of the entire human liver. As long as your model answers the questions you’re asking, and you’re aware of any shortcomings, then it’s still incredibly powerful”.
A global view
Time and research efforts can be invested into developing a more relevant cell model, but that model can’t reach its full potential if the research question isn’t appropriate to solve the health issue for everyone. When identifying a new target, have genetic differences been factored into the study?
Take the F508del mutation, for example. This is considered to be responsible for the vast majority of cystic fibrosis cases globally. Many gene therapies are therefore targeted to this specific mutation. Unfortunately, this mutation occurs in less than 50% of the Black African CF population, creating a discrepancy in treatment efficiency. “Targeting this mutation is still incredibly important, as it can help the majority of patients,” explained Janine. “However, we need to start thinking more about theratypes, and the consequences of disease. It’s vital to have a global perspective when we’re developing new therapies.”
The challenges extend beyond genetics, and disease burden is also a significant factor that needs to be considered for cell profiling. “While there are variants in the liver-metabolising genes that break down HIV therapeutic compounds that are similar in European and Black African populations, a variant that completely disables one of the key metabolising genes that breaks down our current antiretrovirals will massively and negatively impact adverse drug reactions in sub-Saharan Africa patients where our HIV burden is huge,” said Janine.
From these examples, it is clear that changing the way that researchers look at their original question – whether considering genetics, disease burden or the model used – is crucial to rapidly advance healthcare for all. However, changing perceptions and thought patterns is a gradual process, and requires collaboration, continual learning, and openness to hearing new ideas.
The free ELRIG Advances in Cell Based Screening in Drug Discovery event is an ideal forum to begin these research-changing conversations.
Reframing the problem
It’s important – now more than ever – that new advances are shared and scientists are exposed to different viewpoints. Janine hopes that her Keynote, which opens the event, will encourage researchers to look at problems in a different way. “It’s really essential that we alert people to the seriousness of what genetic backgrounds can do in terms of research,” she said. “There was an incredible amount of work that went into the human genome project, and it’s been a life-changing foundation for new discoveries. But imagine where we’d be if we’d looked at the project from a global point of view 21 years ago.”
Speakers at the fourth ELRIG Advances in Cell Based Screening in Drug Discovery event will present different tools and approaches that can be taken to improve cell assay profiling. “I’m looking forward to learning all about the latest advances at the meeting,” said Janine. “For example, the robotics work from Lorna Suckling, GlaxoSmithKline, looks incredible. Also, the image-based drug screening from Berend Snijder, ETH Zurich and cell painting presentation from Slava Ziegler, Max Planck Institute of Molecular Physiology sound really exciting.”
ELRIG Advances in Cell Based Screening in Drug Discovery 2022 is a free in-person event focused on improving and advancing cell assay profiling. From May 10-12 at the AstraZeneca R&D site in Gothenburg, Sweden, researchers across academia and industry are invited to network and share their viewpoints and knowledge to improve success rates in drug discovery.
Change your point of view and register to attend this exciting event today.