This week marks the start of an exclusive interview series leading up to SynBioBeta London 2016. Each week, we will highlight some of the best and brightest minds in synthetic biology and biotechnology.

This week, I interviewed the President and CEO of Circularis, Dr. Paul A. Feldstein.

Circularis is an exciting new biotech company that has an impressive new tool with the power to increase the production of proteins, improve accuracy of diagnostics, and improve targeting of cancer therapeutics. They just finished their time at San Francisco Incubator, IndieBio, and are moving their company to Davis, California over the next few weeks.To start, let me say that the Circularis technology sounds extremely interesting. You make very large and exciting claims about your technology. What area do you see it having the most impact upon?That’s a good question. I’m going to give you a two-part answer.In the short term, things like protein production. We started with a commonly used promoter in E. coli, the T7 . As you know, we have variant promoters that are more than two times better, I think nearly three times better, in terms of protein production. We’ve also shown that actually using a weaker promoter can lead to more protein production. In collaboration with another company, we used a weak T7 and increased protein production by 50-60%. So that’s the first place we expect to have value, and that’s just in bacteria. We’ve also shown our system works in mammalian cells, in CHO cells, and we want to work on finding some tools to be used since CHO cells are so important in the production of biologicals. The next place we want to go, one that is sort of a much longer path to market, is in cancer diagnostics and therapeutics. We’re thinking of promoter profiles as a kind of intracellular biomarker that we can read. That’s where we’d like to go, but we’re just now sort of starting that. My hope is that we will turn that into something interesting. Like I said, we can make protein production more efficient now, and we hope to build off of that.So with all of this said, do you see a new field of study emerging focusing on promoter profiles?Yeah, there is actually a term that sometimes people use called the “Regulome,” which is a term that I think came from a professor at Stanford . The thing about promoters is, in eukaryotes especially, that they’re sort of like the neurons - the integrators of many signals. The signals come in and at the end of the pathway is gene expression. So if we can understand how those signals actually lead to changes in gene expression, there are a lot of possibilities in diseased cells - or even normal cells.I can totally see the parallel between neuron pathways and signal transduction pathways. In terms of feasibility, you’ve mentioned that you’ve seen a 50-60% increase in protein production in bacteria. Do you think this improvement is scalable in terms of modern bioprocessing techniques?I think so. As I’ve said, we’ve shown our system in bacteria and we’ve shown our system in mammalian cells. We’re in the first steps of showing plant proof-of-concept and then moving to yeast , I don’t think we’ll have a problem. One of the things that we can do is look at how promoter activity varies in bioreactors. This has already been done using RNAseq, where one can tell which genes are on and which genes are off in a bioreactor; but our platform can do “promoter evolution” in a bioreactor and that’s how we found the better T7. We can essentially put a million variant promoters at scale in a fermentor and say “which of these promoters is best?” You can’t do that with RNAseq. I think we can have the capability of making a big difference health production environments, not just a lab. It’s definitely possible to find things that are better in a lab, but you don’t know if those are necessarily going to translate into improvements in productions at scale. With fermenters, you have no idea if that promoter is going to work well under those conditions.What do you hope to see most, personally, created as a result of your technology?In the short term, cancer diagnostics and therapeutics is probably the most significant in my mind there’s no question that being able to improve outcomes in patients by being able to look at the differences in promoter profiles of cells is significant. The ultimate goal is to understand, in a complex organism like us , how promoters do what they do. For example, there’s a promoter in sea urchins called the endo16 promoter. It’s only expressed at one time, in one place, in sea urchins during development. It has a promoter that is 2,300 base pairs long. It has all of these transcription binding sites that allow it to essentially function like a simple computer program. It reads off where things are bound, and how much is bound. It is essentially a program that runs , “If something is bound at this site, and at this site, then this happens. If something is bound at a second site and a third site, then something else happens.” If we can come to understand that, the possibilities are endless...and we have a tool that I think can allow us to do that. That’s a very long-term goal. Additionally, it’s unknown what the economic value is, but having a better understanding of how cells do what they do and how complex organisms control gene expression there is value economically and in terms of science. Also in terms of understanding disease and understanding things like cancer. It really does seem like the applications are endless. Switching gears to the business side of the house. You’ve clearly demonstrated feasibility, do you have any more investments or major milestones on the horizon?We’re still working on our seed funding. We have some money from IndieBio. We have a lot of companies that are interested in doing deals with us and we’re in the middle of negotiating those. I can’t say anything more than that. I am hoping that people will see that we are being successful with our clients, which will bring in more clients and money.We just finished and, in fact, we’re temporarily moving to a space in Davis, CA. We’re moving with two other IndieBio companies, Gelzen and Memphis meats. We’re really close with Gelzen and want to work closely with them to help them with their production platform. We’re Memphis Meats as well. The lab won’t be ready for a few weeks or a month. In the meantime, things in minus 80’s and minus 20’s. We’re going back to the little incubator that we started at called the UC Davis HM Clause Life Science Innovation Center.To learn more, come to SynBioBeta London Session 3 at 1:55 pm – 3:00 pm.