Researcher of the Month: Stephen Floor, PhD

Posted: January 17, 2020
By Shelley Wong

If cells are made of molecules that have no agency, how can they make decisions? Stephen Floor, PhD, assistant professor of cell and tissue biology in the School of Dentistry, is interested in the control of gene expression at the level of RNA.

“For many genes, when you turn the gene on and start making RNA, you make protein by default,” says Floor (lab website). “But for some genes, the RNAs that are produced are highly regulated. You can produce an RNA that makes zero protein or you can produce an RNA that makes protein in a context-dependent manner. We’re most interested in this collection of genes that make special messenger RNAs with regulatory information that allows the cell to make decisions in response to the environment and other cues.”

In 2018, Floor was one of six UCSF early-career scientists to receive a National Institutes of Health (NIH) Director’s Award, funded by the High-Risk, High-Reward Research program, part of the NIH Common Fund. One of the major objectives in Floor’s lab is to find a way to use emerging types of RNA sequencing to measure not just the average properties of protein production from mRNA, but how each individual mRNA is producing proteins. There are types of translation or protein synthesis that differ between messenger RNAs on the endoplasmic reticulum and messenger RNAs in the bulk cytoplasm. Developing a sequencing tool capable of such measurement would allow Floor and colleagues to ask questions like whether the percentage of mRNAs producing protein differs depending on their position.

Floor contrasts his background in computer science and physics with the scientific challenges of biology. “You can go back to an analytic theory or a program, and you can diagram and say, ‘If we put these pieces together, it will work like this,’” he says. “Biology is very chaotic. You can write down the best plan that looks beautiful on paper, but because biology is so complex, it’s extremely difficult to actually transition that plan into something that works. And not only is it difficult, it doesn’t always behave in ways that you understand, so taking an idea and realizing that idea is much more difficult in biology than it is in many other systems.”

As an undergraduate computer science major, Floor found his interest shifting from writing video games to science after taking a physics course and learning how essential computers were for scientific experiments.

It’s a marriage of discovering things about the natural world through computation and analysis of datasets.

Stephen Floor, PhD

Assistant Professor of Cell and Tissue Biology

“It seemed like a really exciting way to use the power of computation and it’s still very central to what we do. All of the sequencing generates huge amounts of data, so my lab right now is about a third computational, two-thirds experimental. It’s a marriage of discovering things about the natural world through computation and analysis of datasets,” says Floor.

Floor is a faculty member in the School of Dentistry and a UCSF alum. He admires UCSF for its campus-wide understanding of the value of basic research and the connection between discovery-oriented basic research and human health. He had early experience in being a part of globally impactful research. After working with John Gross, PhD, as a UCSF graduate student, Floor joined the lab of Jennifer Doudna, PhD, at UC Berkeley as a postdoctoral scholar. With the advent of Illumina deep sequencing technology, he says, “I wanted to use the rigorous foundation of molecular biology and biophysics I learned from John Gross to develop approaches to measure not just how one protein makes decisions on one mRNA, but how all decisions are made in a biological process in a cell.”

Doudna, along with Emmanuelle Charpentier, PhD, pioneered the CRISPR-mediated genome editing tool, which has revolutionized biology. Floor found a breadth of researchers within Doudna’s lab, with people working in many areas, from viral infection to mouse brain development to bacterial environmental sensing, creating a dynamic environment and an excellent training ground.

As an early-career faculty member and alum, Floor has found UCSF’s philosophy to be “very supportive,” and he is returning that support in kind as a mentor. He says, “I think that it’s fundamentally our responsibility to mentor, enrich, and support everybody that we bring into UCSF, from the graduate student level to research staff, postdocs, support staff, and faculty. It should be our objective as an institution to have a faculty body that reflects the population of the region that we’re in, and I think that it’s important for all mentors and people that are in positions of power to understand the different approaches of mentorship that are necessary to interface with people of different backgrounds.”

Floor speaks to UCSF’s central challenge of the cost of living in the Bay Area as part of the obligation to support the people who come to UCSF. “We need to be very intentional about making sure that the people that we bring in are able to thrive, and that the cost of living doesn’t prevent people, who are excellent and interested, from attending this institution. Nobody could have predicted this kind of growth, but it’s happened, and it’s continuing to happen. We have the science down, and now the question is ‘How do we support the people that we bring into UCSF to keep them here?’”

With his keen approach to biological chaos, Floor is focused on understanding the variances of RNA and why it matters, while also thinking about how to sustain an institution of excellence in response to outside pressures. Both lines of inquiry require experimentation and collaboration, and Floor is committed to exploring possibilities to achieve success.