We regularly invite scientists to present their research to the Mammoth team. This facilitates collaborations and expands our knowledge of important topics including CRISPR, genome editing, diagnostics, and more. Rather than keep what we learn to ourselves, we’ve decided to share it with you through our Mammoth interviews series. This series features short Q&As with the many interesting scientists who speak at Mammoth. Get ready for some fascinating science and even more fascinating people!
In this post, we feature Rodolphe Barrangou PhD, MBA. Rodolphe is a Distinguished Professor of Food Science at NC State, the first to establish the role of natural CRISPR systems (Barrangou et al 2007), Editor-in-chief at The CRISPR Journal, and an entrepreneur who has started several CRISPR-focused companies.
How did CRISPR first catch your eye and why did you end up focusing on it?
Fittingly, I actually came across a bona fide CRISPR locus in the genome of a bacterium I was sequencing, and assembling. This was not the CRISPR genome editing technology most are familiar with, but rather one of the numerous natural CRISPR arrays found in the genomes of many bacteria. Genome assembly was a lot more manual at the time (circa mid 2000’s) than it is now, and as you can imagine, repeated sequences did not do well in the assembly process. Thus, there was a lot of user-heavy trimming and quality control at the edges of bacterial contigs. The peculiar pattern of the CRISPR array literally caught my eye, and it was visually mesmerizing but also caused some head-scratching. It required some fortuitous observations and a few interesting experiments, but long story short, it took about 2 years to decipher the biological role of this locus and its associated genes: it was a bacterial immune system. It is hard to believe how much the field has changed since.
What kinds of CRISPR-enabled products are you most excited about right now?
Obviously, we are all excited about therapeutic applications in general and gene therapies in particular, with much underway and pending in the clinic. In 2020, with COVID-19 on our minds and a huge testing gap to address, many are also excited about CRISPR-based diagnostics and it is great to see how quickly Mammoth has been able to contribute to this. Personally, however, as a food scientist and an “Ag guy”, I am most excited about bringing CRISPR into the field, onto our plates, and enhancing our foods. CRISPR-enhanced yoghurt cultures have now been on the market for nearly a decade, and I think crop breeding is poised to be very impactul in the short term. If you think about impact, comparing therapeutic needs for a limited patient population versus food needs for every living consumer on the planet, crop breeding is arguably the most exciting and impactful application.
Are there any applications of CRISPR that aren’t getting much attention right now but that you think will be big in the next 5 – 10 years?
I think it is important to balance short-term, mid-term and long-term uses of CRISPR in the grand scheme of things and when I think about big problems that will take time, with all our sustainability challenges today, forestry is obviously “big” and could have the most impact long term (closer to 25 years than the 5-10 year timeline above, but we have to start now). I have been working on this with a dear collaborator for 2 years now and there are tremendous opportunities for bringing CRISPR-based breeding to foresters for healthier and more sustainable forests. While this is intuitive for most people, I was quite perplexed to realize how few people actually work on tree genetics, though the timelines can clearly be daunting to people assessing career paths. As microbiologists, we have the luxury of quick experiments and short timelines, as compared to mammalian studies, but trees take this to a whole new level.
Think about how quickly Mammoth has changed in the past year and now try to project what the CRISPR field will look like in 5 years. Now pretend you are a tree breeder, and imagine you have to multiply your experimental timelines by 10. A tree you plant today might take 8-10 years in the field to showcase phenotypic gains that would convince a forester to plant at large scale. Forestry timelines can span a couple of decades, so we have to find a way to incentivize people to really think long-term and commit to longer timelines. Looking at long term cash flows and NPVs rather than short term sales and ROI will be important for investors, and giving a sense of urgency to address sustainability to scientists and business might be the needed tipping point.
Your professional life has spanned large companies, start-ups, and academia. What do you consider the pros and cons of working in these different environments? Do you have a favorite?
All options have their advantages and caveats, for sure, and I am always most compelled by the sense of urgency of start ups. Large companies have resources and career development opportunities, but also set processes and strategic goals that can stifle innovators, especially in cases where disruptive technologies are better de-risked outside the company. For start ups, I quite enjoy the degrees of freedom, the need for all to contribute in many ways and dynamically assist the whole team to solve whatever the next problem is. I think this is where people learn and develop the most, and I find this exciting and refreshing.
Academia has great advantages when it comes to scientific pursuits and creativity, but I think the system needs a complete reset and that funding needs to be re-designed to focus on translational partnerships that incentivize academics to collaborate with industry. This will help bridge the gap between science and technology on one side and applications and product development on the other side. This is why start-ups are most compelling in my opinion because they are at this nexus, with a true sense of urgency.
What characteristics do you look for when building teams to work on new research projects?
When you start something new, you must have adventurous people who are creative and excited about exploration, but who also have an appetite for failure. I want people who have shown the ability to create new paths and blaze new trails, and who have been willing to embrace new technologies, new applications, and new ideas.
I also think people under-estimate how important it is to manage uncertainty. When you start something new, it is not always clear where things are headed and whether things you hope for will work. As a result, re-setting, pivoting, or taking a step back to take two steps forward in another direction is very important. I look for people who have done this anywhere in their previous endeavours.
People who have good interpersonal dynamics and management skills can also have a huge impact. Obviously, team-work and the ability to go through challenges with others is critical, but this is something people often have to learn. It can be much “safer” to learn this in an academic setting where there is less urgency.
Many researchers have a good understanding of what PI’s and industry scientists do, but they may not know what goes into being Editor-in-chief at a journal. How did you become Editor-in-chief at the CRISPR journal and what kinds of day-to-day tasks/challenges do you tackle in this role?
The CRISPR Journal was really Kevin Davies’ idea, and he reached out to me (and presumably a couple of others in the field). I loved the idea (there was a gap in product offering and surely an addressable market), and Kevin and I hit it off early, so it seemed like a no-brainer experiment to try out. As you can imagine, making calls when editors and/or reviewers disagree is perhaps the toughest challenge, and providing a timely decision can be a challenge too. Authors always start the clock when they submit the paper, but it can take way too long to secure reviewers and chase down referees who do not share our sense of urgency. I have quite enjoyed being Editor-in-chief and learning about the details behind some of the interesting aspects of publishing like cover art, front matter, and putting together the portfolio for indexation. Sometimes, it is the issues that you do not anticipate that turn out to be interesting problems to solve.