Research When Away from the Bench: A Conversation with Dr. Colles Price

BY Iris Fung
April 20, 2020

Colles Price, M.S., PhD is a Research Fellow in Medicine at Dana Farber Cancer Institute, Harvard Medical School, and a Postdoctoral Scholar, Cancer Program, Broad Institute. He is currently identifying and validating targets from the Cancer Dependency Map. In particular, he is interested in understanding the anti-cancer effects of hypoxia-related genes and how polar-related genes control cell proliferation and viability. We had the chance to sit down with him and learn about how COVID-19 is affecting his research.

Q: What work have you been doing, now that you can’t be in the lab?

This has been a great time to think through all my projects. My PI (Principal Investigator) has been supportive of us doing a lot of experimental inventory, planning, and reading. Even from before I joined the lab, he’s always recommended taking 2-3 months of just reading and research before doing any experiments. I feel like I’m returning to that time.

This is a hard time for researchers that are always pipetting. But if you take a step back, re-analyze, and look at things with fresh eyes, that takes time. I could easily take up 2-3 months staying at home, not doing any experiments, and still be moving my project forward. It’s hard, because people are so used to doing.

I’ve talked to some of my colleagues about this. One of my colleague’s philosophy is that, at the end of the day, go pipette something. Go do an experiment. My philosophy, and my PI’s, is the opposite: think about it. If you wait a month, and you do that one right experiment, that can be better than doing a month of meh experiments because that one right experiment will give you the right answer.

Q: What would you tell the scientists that share your colleague’s philosophy, rather than yours?

I think this is a good time for those scientists to challenge themselves. They can plan even further ahead than they normally do and think about, “If I do this experiment, how do the results look? What answer will I get?” If you do Experiment A, you should expect that your ideal results will look a certain way. But if they don’t, and they look like B instead, what would that mean? And how can you test that? This takes a lot of time, and people often forget about that.

I would also tell them that having this break is not as bad as you might think because if you do take the time to think everything out, you can go back in 2-3 months later and hit the ground running pretty fast. You’re still advancing your projects, which is important because we’re all funded by grants and money that require it. Even during this time, we’re expected to move projects along, and people forget there’s more than one way to do it. It’s hard, because we often spend 60-80 hours a week pipetting. It’s hard to pause and realize woah, there’s other aspects to this I can think about and do.

Q: Have folks in the Cancer Program talked about what they can do with their skills and knowledge to aid COVID relief efforts?

We’ve had multiple open conversations about it. Todd Golub has worked with the Broad’s Center for Development of Therapeutics (CDOT) and Repurposing Library to see if any compounds currently in the library had any effect on viral infection. Some of the immunology labs have been looking at immunity. Some of the research associates have volunteered to get trained to work with the team at the Broad that is conducting testing.

Q: Tell me more about the RAs (Research Associates) that are volunteering to get trained. What’s the driving motivation for them to do so? Frustration? More free time?
It’s a combination. People – not just the RAs, but everyone around – definitely feel a frustration, some amount of, “there’s a big thing happening and I’m stuck at home.”
People – not just the RAs, but everyone around – definitely feel a frustration, some amount of, “there’s a big thing happening and I’m stuck at home.”

Michael Wells (Postdoctoral Fellow, Broad Institute) started a sign up sheet and created a big database of researchers who are willing to help with COVID-19 efforts. There’s a lot of people that want to help. I’ve felt it too. I want to help, but I don’t work in infectious diseases, which is tough. But I also see that there’s a lot of really smart people working on this, which gives me hope. The number of published PubMed articles about COVID-19 is in the thousands already. That’s not even including preprints. There’s a lot of great people working on this.

Q: While the Broad has asked a majority of its employees to work remotely, I know the Genomics Platform (GP) has turned into a diagnostics testing space. What other labs are currently still running at the Broad?

The Sabeti lab, which is the infectious disease lab, is still running. They played a big role in the Ebola research during the 2014 outbreak. Feng Zhang still has his lab going at a reduced capacity, which is cool because they developed the SHERLOCK approach. I think there’s a few people in Feng’s lab that are trying to work on that with the Sabeti lab to optimize it for COVID testing.

Q: Why testing specifically? Why not looking for a vaccine or cure, like many biotechs are?

One of the things to note – we talk a lot about COVID testing. One of the big challenges is the variety of detection kits available. Each kit has a very, very different detection threshold. Abbot’s detection kit, which is called Abbott Realtime SARS-COV2 Assay, has a limit of detection of 100 copies per mL. Which is great – it’s really really sensitive. However, many of the earlier tests were far less sensitive. The original CDC assay only detected something like 3200 copies per mL. LabCorp’s COVID19 RT PCR test can only detect 6250 copies per mL. That’s already 60 fold less than Abbot’s. The problem with this is that you only test positive on these tests if you already have a pretty high disease burden.

Imagine if you got the test on day 1 of being infected. The sensitive tests would tell you that you’re infected on day 1, and thus your likelihood of infecting other people goes way down because you’re detecting it almost right away and taking preventative measures. The sensitivity can make a pretty large impact on the spread of a disease.

The sensitive tests would tell you that you’re infected on day 1, and thus your likelihood of infecting other people goes way down because you’re detecting it almost right away and taking preventative measures. The sensitivity can make a pretty large impact on the spread of a disease.

Since then, some places have updated tests. Quest Diagnostics has an RT PCR assay that can detect 136 copies per mL. So it’s gotten better. But that’s one of the reasons why I think the Sabeti lab, and Feng’s lab, are working really hard on these testing assays. There’s a huge potential to make an impact there.

The Broad’s expertise, specifically in GP, is throughput. We may not be able to go as deep as everyone else, but we can do high numbers. They have automated robots and have been able to repurpose most of the equipment and space for testing. They’re focusing almost exclusively on COVID, and they’re currently processing nearly 1000 tests a day, with a turnaround time of ~72 hours. They’re running four teams to do it too, which is kind of crazy. They pair a day team and a night team, and these two teams work 3-4 days before they swap out with the second set. This lets them run almost 24/7.

That’s pretty awesome.
It is pretty awesome. Like I said, it’s not always the most sensitive, but it’s high throughput. It’s definitely the Broad approach – let’s ramp this up to 1000, let’s do this. With that amount of tests, you can really start screening people pretty well.

It’s really difficult to take a step back, reevaluate and reassess when so much of our training is constantly being at the bench.
Q: Do you see this period affecting how bench scientists do science?
I really hope so. I hope 1) it teaches bench scientists that there’s benefits to being thoughtful about their experiments. I hope it’ll teach them to do the right planning around how to do things and what the right way to do things is. It’s really difficult to take a step back, reevaluate and reassess when so much of our training is constantly being at the bench.

This is a good lesson for all of us around how to do that, and I hope it makes all of our science better. I also hope that 2) this time will allow people to learn computational skills, and learn how to incorporate it into their research. It’s a good time to take a statistics class, or learn R, or learn Python. You don’t have to be an expert, but it will generally make your science better. You also see people looking at online public databases way more now than they ever used to. I think this increase will probably stick.

I don’t think there will be big change to anything in the short term, but I think we will see changes in the long term as we have a wave of people come in who have been at home and now they know how to be scientists even remotely, and approach thinking about science more mindfully.

Q: Lastly, outside of progressing your research, have you developed any new routines while working from home?
Yeah, I have two kids so I’m spending a lot more time with them. I’m keeping up with their school work since school is now over Zoom. I’m also trying to get back into playing piano and I’ve been teaching my son fun songs like High Hopes by Panic! At The Disco since he really likes that song. But getting them to sit and play piano is hard. I’ve also had fun teaching them watered down versions of lab protocols- we’ve pipetted things together, made and ran a gel together, did some PCR using water baths.

Published by Iris Fung
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