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August 16, 2022

Interview: Olivia Rissland

Olivia Rissland is a associate professor in the Department of Biochemistry & Molecular Genetics at the University of Colorado School of Medicine. She has made groundbreaking discoveries in the field of RNA biology that illuminate how genetic regulatory information is interpreted by the cell. She has discovered several molecular pathways that cells use to turn genes off, which have profound implications on both development and diseases like cancer where these pathways are disregulated. She was awarded her D. Phil. from the University of Oxford, where her studies were funded by a Rhodes Scholarship, and she received postdoctoral training at the Whitehead Institute. She has been recognized with a prestigious CAREER award from the National Science Foundation as well as being an NIH-funded investigator.

How would you describe your research to a layperson?

Our DNA can be thought of as a cookbook, full of thousands and thousands of recipes for different dishes that, in turn, can be combined to make many different meals. Each cell in our body follows some of these recipes to make the dishes it needs, and what makes one cell type (like a skin cell) different from another (like a liver cell) is what recipes are used and what dishes are made. To put this more technically, each recipe is a gene, and the eventual dish is a protein.

My lab works on understanding how cells control what recipes are followed to ensure that the right dish is made in the right place at the right time. More specifically, we look at this at the level of messenger RNA, which (in addition to being the basis of many COVID-19 vaccines!) is a naturally occurring molecule and an essential intermediate for following the cellular recipes. We ask how messenger RNAs are made and destroyed, and how these processes contribute to making the right protein within each cell.  

Describe your experience with science funders (private foundations, NIH/NSF/etc.). What do they do right? What could they improve? 

One of the joys of academic research is the freedom to go where intuition and curiosity take us in our quest to understand life. Many researchers are explorers—only unlike the ones who tramped through forests and mountains, our vistas are of the molecular universe. In my opinion, allowing fundamental researchers to follow the unexpected discoveries and puzzles—that is, to be explorers—should be one of the goals of science funding. In this respect, the MIRA program from NIGMS is a good example: it funds an overall research “program,” rather than a specific project, and so researchers can feel less tied to specific experiments that they might have proposed several years earlier. (In the interest of full disclosure, I received a MIRA grant in 2018.)

Unfortunately, following your curiosity also requires enough money to run the experiments! One challenge of the MIRA program is that the budgets are not high enough to meet the financial demands of research in 2022. For instance, for early stage investigators, the budget is the same as the modular R01 budget ($250K per year). However, that budget amount was established in 1998 and has roughly half the purchasing power in today’s dollars. That makes the calculus of lab budgets very different for lab heads starting today than those who started 25 years ago.

Another challenge of the NIH system in general is that it is not very responsive because there is typically at least a 9- to 12-month gap between submitting a grant application and receiving funds. The ability to get smaller grant funds more quickly would be transformative. One program that seems to be doing this well is the ISAC program (supported by NIDDK and from which I recently received a grant). The turnaround time for my application was three months, and it has accelerated our ability to work on a new project. Implementing these types of mechanisms would help researchers be more nimble in exploring new and exciting research directions.

Surveys show that scientists say they spend upwards of 44% of their time on proposals, reports, IRBs, budgets–that is, administrative and regulatory requirements. Is that consistent with your experience? Is there anything that could be streamlined?

Happily, because of the types of experiments my lab does, I do not spend a large fraction of my time on IRBs, budgets, and reports, although annual reports could certainly be streamlined.

If you didn’t need to please funders or publish journal articles, is there anything that would be different about your research agenda?

I would like to think that we’ve remained true to our curiosity in our research agenda! And certainly, having a MIRA grant and institutional start-up has helped make that happen. But the pressure of publishing and funding renewals can make long-shot projects much riskier for our long-term budget outlook. Having to demonstrate expertise in grant applications can also make changing research directions harder and has been inhibitory to us exploring some cool RNA questions in new biological contexts.

If you could change the organization or management of universities, what reforms would you recommend?

Unrestricted funds are very important. In many institutions, these primarily come as a part of a start-up package (as in my case) or as a retention package. For my lab, our start-up funds have enabled new directions for our research, and they have also funded new equipment when it has necessary for expansion or for replacing broken equipment. Having start-up funds has also ensured that I can make good hires when an exceptional scientist comes along, irrespective of having a new person “budgeted” on one of our grants. In other words, unrestricted funds are an engine that catalyzes our success. Obviously, institutions also have budgets and many demands on the available pools of money, but finding ways to provide scientists with some unrestricted funds will give researchers the freedom and opportunity to do the best science. 

Just for fun, is there any specific paper published in your field in the past 1-5 years that you wish you could have published?

In my opinion, we are in the Golden Age of RNA biology, and so there are many papers that I wish I could have published! One of my recent favorites is: https://www.biorxiv.org/content/10.1101/2021.11.03.467131v1 from Andrea Pauli’s lab about developmental control of the cellular protein-making machine (which is called “the ribosome”).