DtoR aims to produce tools to “tune” protein production. The team has developed the PCR of gene expression—a disruptive technology that will revolutionize the tools used to “tune” protein production in any organism. In one step, and for any cell type, it can identify all of the switches regulating expression of the genome, as well as how active they are. It can also rapidly evolve or synthesize new switches to adapt to any application.
Applications developed using their platform will lead to improved product yields in bioreactors, engineered specialty crops, optimized cancer therapeutics, and much more.
The founders and the Team
DtoR is an incubator out of UC Davis-HM.CLAUSE Life Science Innovation Center. The company was founded by Dr Paul Feldstein, Dr Jim Lincoln and Dr LeAnn Lindsay.
The startup journey
Initially, Jim and Paul started the company in November 2014 and then Lindsay joined in later as a co-founder. They had interest in working with promoters and thought that there must be a better way to find and work with promoters. Jim and Paul talked about this for years before going to the drawing board and sketching out their technology. They then recorded the invention with UC Davis and started looking for funding and came across SBIR (Small Business Innovation Research Grants). While boot-strapping, they applied for a few grants and also to IndieBio’s program. They got selected in IndieBio’s second cohort and been with them ever since.
Paul: So imagine taking any organism, even an unknown organism; we can essentially recover the relevant sequences in one step. We can also take a known promoter sequence, re-utilize it and run it back through our system and look at the population of promoters that are produced, and tell which are stronger and which are weaker.
One of the things, for example, is we can find promoters that are turned on by particular treatments, or turned off as well. We have taken human promoters and simply made a library of all known human promoters using what we select from our system. These were then then put into cancer cells to see which of these promoters turn up or turn down genes. We can even use it to map cohesion in the cancer gene, using the tumor gene, by looking for promoters that disappear completely. This is the sort of healthcare that we are looking towards in the future.
One of the things we can do with our technology is building diagnostics by essentially doing a promoter profile of different tumor cells and look at what changes. Right now though we are mostly focusing on synthetic biology, therapeutics is our ultimate goal. We want to produce therapeutic proteins and so on.
Most of our work has been completed invitro in animal and human cells and in plants. I am a nuclear chemist, and a virologist by training. Jim Lincon is our plant person, he has a lot of plant biology experience and Lindsay has experience in animal and cell biology.
One of the things that we are interested in doing in plants is metabolic engineering; essentially what we want to do is to produce a micro nutrient in plants that is normally added externally. The plant we are interested in is Alfalfa. We are planning to find all the promoters in Alfalfa and then we are going to use promoters of different strengths to essentially tune the production of the said micro nutrient to exactly match the government limit. The government says you can only have so many parts per million (ppm) of the micro nutrient in feed/animal feed, and so what we can do is, by choosing promoters of different strengths, we can produce just enough of protein to produce exactly the amount of the micro nutrient that the government will allow and then the grower won’t have to add it externally. They can simply grow the Alfalfa and feed it to their animals and it is ready to go as it is! That is sort of an application that we are very interested in, and it will also then demonstrate our ability to find and if necessary, evolve promoters.
We want to eventually work on Cyanobacteria for biofuels, bioreactors, diagnostics, vaccines and much more.