Our trainees review webinars in their given fields and share abstracts to help colleagues outside their discipline make an informed choice about watching them. As our program bridges diverse disciplines, these abstracts are beneficial for our own group in helping one another gain key knowledge in each other’s fields. We are happy to share these here for anyone else who may find them helpful.
Selina Wray, PhD – Professor at University College London
July 8, 2021
British Neuroscience Association
The British Neuroscience Association hosts a webinar series with the goal of strengthening credibility in neuroscience. This seminar, from Selina Wray at University College London, focuses on reproducibility and robustness of in vitro models. Additional considerations and best practices when using human induced pluripotent stem cells (IPSC) for disease modeling are presented. Wray’s lab studies Alzheimer’s disease, so throughout she provides insight into her own lab’s struggles and triumphs when modeling disease.
Wray begins with a quick introduction to IPSCs noting how this technology has advanced neuroscience capabilities; however, this technology is not without its challenges. Wray notes we must be aware of these as it is often hard to acknowledge the downsides of new and innovative technologies. To properly address these challenges, certain questions need to be answered when planning IPSC studies. Wray cites the following as the most common questions:
- Should I use patient-derived cells or isogenic controls?
- How many lines and how many clones do I need?
- What is the best way to make neurons?
- How many differentiations are needed?
The biggest challenge facing these studies, according to Wray, is the degree of variability in IPSCs when using patient-derived cells. To address this variability, it is best to use the most patients possible, with the minimum being 3 donors and 3 controls. While this variability is a challenge, it is also powerful for understanding clinical heterogeneity and disease modifiers. Alternatively, isogenic cells allow for creation of genetic variants that don’t naturally occur. They also provide multiple points of comparison serving as a compliment to patient-derived cells. So, the question remains, patient-derived cells or isogenic controls? Ideally, both types of lines would be used to get the fullest picture of your disease model!
Once people have their cells, they often ask what the best way is to make them into neurons. Wray’s answer is that there is no best way, but you need to determine which differentiation strategy is most appropriate to address your research question. She cites a variety of strategies that may provide different outcomes and even uses research from her own lab to show how these strategies impact results. Still, no matter which strategy is used there are some best practices that Wray recommends. The practices include having quality control checks at every step, buying bulk reagents for consistency across experiments, and using orthogonal approaches to increase confidence in cell phenotyping.
Throughout Wray’s seminar, she provides insight into how these strategies provided differences in robustness and reproducibility in disease models. She backs up her statements with published research from her own lab. She also provides citations to other resources which may be helpful for producing these models in your own lab. Credibility of scientific research is vital to maintaining trust in science. This seminar is a great place to start learning how to strengthen the credibility of your in vitro experiments with improved reproducibility and robustness. For more advice like this, check out the latest installments of this series on the British Neuroscience Association’s YouTube channel. From data handling to shifting research culture, these webinars cover a range of topics important to scientific credibility.