Welcome to The Microbiome Coalition's Speed Round series in which we ask key opinion leaders a single question about the latest happenings in the microbiome sphere. We hope you enjoy!
In this Speed Round, we feature Peter Christey, Co-founder and CEO of General Automation Lab Technologies (GALT).
TMBC: Do we need to expand beyond sequencing as the primary tool for studying the microbiome?
Christey: Sequencing is an incredibly powerful tool that has helped illuminate the wonderful complexity and richness of the microbiome. It’s one of the few, if not the only, research tools we currently have that scales to the complexity of the microbial systems we are studying.
But is it enough?
Many of the microbiome-oriented presentations and publications we see in the literature are almost entirely sequencing-based. The typical study takes samples from both healthy and diseased patients, performs next generation sequencing on the microbiome, and compares results. Charts are presented showing that population x goes up, population y goes down. Principle component analysis (PCA) and other statistical charts are provided to demonstrate some point or other. What is missing is the punchline, the insight that helps explain what is going on. What is the microbiome doing? Who are the key actors? How are they impacting the disease state? How is the microbiome interacting with the host? What is the underlying biology and chemistry here? And critically, are the changes we observe causative in the disease we are studying, or rather a consequence or complex admixture of virtuous and negative feedback mechanisms?
I don’t believe sequencing by itself can take us to the next level of understanding.
We are doing the equivalent of trying to cure cancer solely by sequencing a million tumor samples. Cancer is being defeated by insights derived from multiple avenues of investigation, including clinical trials, epidemiological data, analysis of the underlying genetics, and “at the bench” cell biology to dissect the core biological mechanisms and pathways. We need to harness all of the tools we have available to us to understand what’s going on in a microbiome, and where necessary develop new tools that are unique to our needs.
One area where there is huge unmet need is in the microbiome research wet lab. Bench work is critical to test hypotheses and new ideas under controlled conditions – the path to getting from correlation to mechanism. Microbiome bench work is constrained by the current toolset. Mainstream technologies were invented over 100 years ago. Core tasks, such as isolating target microbes, creating comprehensive strain collections or studying model ecosystems, are often difficult or impractical. We need new tools to break through the current barriers to accessing and studying microbes. New tools will build upon and be a force multiplier for the insights we generate from sequencing based studies.