News from the Fraser Lab

A long overdue update

James Fraser
10 November 2017

It’s been over a year since I wrote an update for our lab news section (parenthood has slowed me down a bit). There have been a lot of changes:

  • Goodbye David Mavor, PhD!
    • David (aka Iggy) finished his doctoral work in the lab and moved on to Dan Bolon’s lab at UMass Medical. Iggy merged his thesis work with graduate education in the PUBS course and published a spectacular deep mutational scanning paper (with a record number of co-authors!) based on the the first year of the class. The next two years were summarized in a pre-print. Congratulations Dr. Mavor
  • Welcome to new postdocs Dr. Brandi Hudson (and soon Dr. John Lee)!
    • Brandi joined us last summer from the Tantillo lab at UC Davis and has been working in collaboration with Relay Therapeutics and Schrodinger on how to account for conformational dynamics in ligand design. John will be joining us later this month from the Burkart lab at UCSD.
  • New rotation students!
    • Two fantastic students are rotating with us this quarter. Jenna from iPQB and Robbie from Tetrad. Jenna is working with Erin Thompson on compensatory mutations in enzymes and Robbie is working with Ben Barad on chitinases!
  • Foreign visitors to the lab!
    • During 2016 we had Tommy Lazarou visiting from Canada as part of his co-op program at McMaster University. He’s now a graduate student at NYU. Dr. Kazutaka Ito recently joined us from Asahi KASEI Pharma Corporation in Japan and will be working with Michael Thompson on proteases and XFELs (including our trip later this month to the SACLA XFEL in Japan). Early next year, Prof. Roberto Chica will be joining us on sabbatical from University of Ottawa to work on room temperature X-ray diffraction studies of designed enzymes. I love the international community of science. Visiting the Tawfik lab at the Weizmann Institute in 2010 was a formative experience for me, so it’s fun to host people here and continue the tradition of scientific exchange!
  • Goodbye Professor Daniel Keedy!
    • Postdoc Daniel Keedy accepted a tenure track position in New York, NY at the ASRC of CUNY as part of their Structural Biology Initiative. We held his goodbye party this week and he has already started his long drive across the country. In our lab, supported by the A.P. Giannini Foundation, Daniel pioneered new computational and experimental approaches to “map the intramolecular nervous systems of proteins” - a synthesis we’ve come to call multiconformer multitemperature X-ray crystallgoraphy (or MMX). Daniel always had a remarkable way with words and his attention to detail was second to none. He took a big chance coming to join a fresh new lab and I’m so proud of all that he accomplished here. His last manuscript is almost ready to post on BioRxiv and we’re excited to see how Prof. Keedy adjusts to being the “big cheese” of the Keedy lab in 2018.
  • Starting a new “Macromecular Structure Methods” class!
    • John Gross and I have started a new class for UCSF Biophysics and Chemical Biology students. In the tradition of PUBS, this new Methods class has a project-based format. Organizing the material has invovled a lot of heavy lifting by David Bulkley (in our EM core), Ryan Tibble (in John’s lab), Eugene Palovcak and Daniel Asarnow (in Yifan Cheng’s lab), and Kazu Ito and Michael Thompson (in our lab!). It is a lot of work to start these kinds of classes, but I think it is worth it. I’ll update with an assessment later in the year!

On being quoted in the NYT, Preprints, and Beer (and Tacos)

James Fraser
16 March 2016

At the ASAPbio meeting, I talked about the importance of building a lab culture as a junior faculty member. Two of the most important things about the culture we are trying to build in the Fraser lab are: 1) we have high scientific standards and 2) we enjoy communicating our results. Preprints help us with both. We set a high standard by showing the world our results when we are ready by posting a preprint, not after weeks or months in review. We also do this because we hope that other scientists will give us feedback and build on our work. We celebrate posting the preprint (which we do simultaneously upon submitting to a journal, but more on that later) because we want to congratulate each other on the hard work that went into the paper. Preprints return the control over both of these important aspects of culture to us, the scientists.

In articulating these aspects of our lab culture, I also mentioned our lab motto: Beer and Tacos. Now that this phrase has made the New York Times, I thought I might explain the history of “Beer and Tacos”. My attraction to this phrase has its origin, like many of my scientific interests, in baseball statistics. In 2003 (when I was an undergraduate at McGill), Dayn Perry used the “Beer and Tacos” analogy in describing the false dichotomy between data driven analytics (sabermetrics/statistical analysis) and observational scouting (which is more qualitative). Perry’s story was in part motivated by a grumpy article written by my hometown baseball writer Richard Griffin. Although I’ve never actually confronted Griffin about it, I think I may have played a small part in Griffin’s motivation for writing the article. A few days before his article appeared, I was on the field at the SkyDome prior to a Blue Jays game filming a brief segment for the Discovery Channel Canada on baseball statistics (unfortunately, I can’t find the video online!). Griffin walked by, shook his head, and continued on his way. Griffin hated analytics and loved scouting.

At the time this was a bit of a holy war. It is dramatized in the movie Moneyball, based on the excellent book by Michael Lewis. In recent years, the value of analytics has been proven time and time again not only in baseball, but also in other sports and even in finance, marketing, etc. However, part of the reason that analytics keeps permeating more and more areas is that there is an intense drive to capture the qualitative aspects and turn them into something quantitative. It is no longer sufficient for a scout to say that an outfielder “tracks the ball well”. This skill wasn’t captured that well in 2003 by simple counting statistics like range factor, but now we can plot the actual path the player takes to determine whether he takes the most efficient route to the ball. What does “beer and tacos” mean? Dayn Perry said it best. In responding to Richard Griffin and others who argued that organizations such as the Boston Red Sox, run at the time by Theo Epstein, should focus less on stats and more on scouting, Perry wrote:

“Grumps like Griffin don’t understand the concept of synergy. A question that’s sometimes posed goes something like this: “Should you run an organization with scouts or statistics?” My answer is the same it would be if someone asked me: “Beer or tacos?” Both, you fool. Why construct an either-or scenario where none need exist? Heady organizations know they need as much good information as possible before they make critical decisions. Boston under Epstein, for example, is a veritable clearinghouse for disparate ideas and perspectives, and so far it’s working just fine.”

From 2005-2010, I was in graduate school at UC Berkeley. When my graduate advisor, Tom Alber, would suggest multiple experiments during group meeting, I would often yell out “Beer and Tacos” from the back of the room. The idea being that we shouldn’t prioritize only experiment A or experiment B, but that we should probably consider doing both. In 2011, when I started my lab, I continued shouting “Beer and Tacos” in my own group meetings at UCSF. We want to create “a veritable clearinghouse for disparate ideas and perspectives”.

Now we come to publishing. People like Mike Eisen argue for BEER (only immediate publication/preprints and post publication peer review/PPPR) and people like Emilie Marcus argue for TACOS (only traditional journals, unless you have a special “wink wink” agreement). The system is evolving. It’s clear that “journals only” is not going to be the future. The delays and politics around “formal peer review” can be detrimental to our goals as scholars. However, many of the trends on how journals are coordinating peer review are all about openness, speed, and scholarship. It’s also clear that journals can add value, even beyond the obvious benefits in coordinating peer review: reading the table of contents is (surprisingly) the nearly exclusive way that many scientists become aware of work outside their lab. Becoming aware of papers in this manner is not the ideal system in the long term, but it does add value today. The exact pairing of preprints and journals is in flux - but there is wide agreement that we value scholarship and rapid communication of results.

As we debate exactly what type of beer we will be drinking in the future and what filling should go in the taco, my lab cares about getting our work out there as quickly as possible and ensuring that it reaches the widest audience possible. So we ignore shouts for “Beer OR Tacos” and choose “Beer AND Tacos”. When we post preprints, we are happy about getting our work out there immediately, we are eager to improve the work through peer review in any form, and we are hopeful that eventually publishing in a traditional journal will help it find an audience. And so we go to celebrate, as a lab, by ordering “Beer and Tacos”.

Summer's Gone

James Fraser
23 August 2015

almost… it’s been a bit too long since we updated the website:

  • Erin joined the lab!
  • Lin came back from parental leave!
  • Andrew completed the Insight Data Science program!
  • Alex and Pooja rotated!
  • Saul was a great SEP student!
  • Jennifer did great lab work and updated the lab cartoon!
  • We published a bunch of papers!
  • Joslyn got promoted and Eleanor took over our admin responsibilities!
  • and we started planning for this year’s version of PUBS

Welcome new UCSF Faculty Fellow Joe Bondy-Denomy

James Fraser
12 May 2015

A warm welcome to new UCSF Faculty Fellow Joe Bondy-Denomy. Joe was a graduate student with Alan Davidson at University of Toronto, which is also the lab that gave me a start in science as an undergraduate. The Bondy-Denomy Lab builds on his groundbreaking discovery of naturally occurring anti-CRISPR proteins that antagonize the CRISPR systems that are all the rage in genomics. Welcome Joe!

Welcome Joe Bondy-Denomy

Spring quarter has sprung

James Fraser
22 April 2015

A belated welcome to our new rotation student Eugene!


And farewell to Erin and Evan who have moved on to their final rotations in the Gestwicki and Frost labs, respectively…

We are apparently on a roll of rotation students with first names that start with the letter “E”…