May 29, 2015
Dear Friend of the UW Institute for Protein Design:
On behalf of the UW Institute for Protein Design (IPD), I wish to thank you for supporting our shared vision to design a whole new world of synthetic proteins that address 21st century challenges in medicine, energy and technology. It is my pleasure to provide you with an update on how your generous contributions are enabling us to make key investments in the IPD and progress in our work.
IPD Advisory Board
In January, we announced the formation of the IPD Advisory Board, which includes four distinguished professionals from the fields of pharmaceutical development, finance, venture capital, and synthetic biology. The formation of this advisory board is an important step in the development of the IPD, and we are honored to have the benefit of guidance from these experts.
The IPD Advisory Board includes: Tadataka (Tachi) Yamada (chair), former executive vice president and chief medical & scientific officer and current board member at Takeda Pharmaceuticals; George Church, professor of genetics at Harvard Medical School, director of PersonalGenomes.org, and pioneer of synthetic biology research; Peter Goodfellow, geneticist and former senior vice president of Discovery Research at GlaxoSmithKline who now serves as advisor to the venture capital company Abingworth and as a board member of several companies and medical charities; and Bryan White, managing director and chief investment officer of BlackRock Alternative Advisors, private investor, and member of several charitable organizations.
In addition to the Advisory Board, the IPD has assembled a team of local prominent scientists, chaired by former Dendreon CSO David Urdal, to be part of the IPD Scientific Council.
Translational Research Center
In June 2014 the IPD established its Translational Research Center, which is operated with a $1.4 million Opportunity Grant from the Life Sciences Discovery Fund (LSDF). The LSDF funding to the IPD was matched 4-fold by generous contributions from private donors ($3.2 M), UW ($1.4 M), and the Washington Research Foundation ($1 M). The translational research center serves the important role of supporting projects that convert scientific breakthroughs from IPD labs into commercially viable products. The center prepares outstanding young scientists to commercialize these breakthroughs and establish start-up companies in the Seattle area.
This month Cyrus Biotechnology will be the first start-up company to graduate from the IPD Translational Research Center. The company was co-founded by two postdoctoral fellows, Drs. Lucas Nivon and Yifan Song, along with graduate student Javier Castellanos who completed his Ph.D. work in the Baker lab in late 2014.
With seed financing from the W-Fund and the WINGS angel investor group, Cyrus is launching a new web-based interface to enable biopharmaceutical companies better access to the power of Rosetta protein structure prediction and design through a user friendly software-as-a-service, cloud-based solution. Located in Seattle’s South Lake Union area, Cyrus is an important part of the growing healthcare innovation network, as they work to empower the design of new medicines that can only be discovered with the help of Rosetta.
Our other translational investigators include Dr. Ingrid Swanson Pultz and Dr. Neil King, both of whom continue to make great progress in their projects.
Dr. Pultz has improved the activity and manufacturability of KumaMax, an award winning computationally designed enzyme that breaks down gluten in the stomach before it gets to the small intestine where it can cause inflammation in patients with celiac disease. Based on her progress, Dr. Pultz was recently awarded a competitive $250K proof of concept matching grant from the LSDF to conduct animal efficacy studies and safety testing of the lead KumaMax variant, an effort which is being matched by an additional $176K in philanthropic donor funding.
Dr. King is developing new protein nanoparticle technology for vaccines and drug delivery, and his growing team of talented researchers has recently demonstrated the ability of computationally designed nanoparticles to deliver packaged proteins into target cells. This breakthrough is garnering considerable attention from the biotechnology venture capital community.
Washington State Priority
In the last update, we mentioned that Governor Jay Inslee’s 2014 Supplemental Budget (4-13-13) included $1 million to support the IPD mission, enabling the UW to recruit a talented computational biologist, Dr. Frank DiMaio, to join the IPD as an assistant professor in the Department of Biochemistry. Two more basic science faculty will join Dr. DiMaio at the IPD over the next two years.
In early May, IPD Translational Investigator Dr. Ingrid Swanson Pultz was invited to participate in a panel discussion chaired by Governor Inslee entitled “The Future Is Bright: Washington State Government Support for Health Care and Life Sciences Entrepreneurs.” Dr. Pultz and four other life science and healthcare entrepreneurs were able to share their stories with an audience of 200+ gathered at the Cambia Grove.
Washington state funding has also enabled the IPD to launch a series of Mini-Symposia in protein design research where we invite internationally recognized protein design experts to talk in an open lecture format to the entire Seattle research community, and then spend the day at the IPD discussing collaborative research projects. Previous speakers have include K. Christopher Garcia, Ph.D. (Stanford University), Timothy Springer, Ph.D. (Harvard University), Bill DeGrado Ph.D. (University of California, San Francisco), and Gevorg Grigoryan, Ph.D. (Dartmouth College).
In addition to our Mini-Symposia, the IPD has welcomed a number of scientists from academia and industry to share their research and discuss potential collaborations. In the past six months, these visitors have included Rogier Sanders, Ph.D. (University of Amsterdam), Jim De Yoreo, Ph.D. (Pacific Northwest National Laboratory), John Platt, Ph.D. (Google Research), and representatives from Sangamo Biosciences (Richmond, CA) and Calico (San Francisco, CA).
Bill and Melinda Gates Foundation Awards for Next Generation Vaccine Design
This January, the IPD was awarded $12 M in funding by the Bill & Melinda Gates Foundation to support vaccine research. Over the next four years, the IPD will lead three international collaborations in the application of computational protein design to next generation vaccines and adjuvant technologies to address the challenges of HIV-AIDS, respiratory syncytial virus (RSV) and the related human metapneumovirus (hMPV). Your philanthropic support for the IPD has made it possible for us to make key investments in immunogen design and protein nanoparticle designs.
These BMGF projects have enabled the IPD to initiate collaborations with world class vaccine researchers from The Scripps Research Institute (La Jolla, CA), Weill Cornell Medical Center (New York, NY), The University of Amsterdam (The Netherlands), Duke University (Durham, NC), and Institute for Biological Research (Italy), along with commercial partners Kymab (Cambridge, UK), CureVac (Tübingen, Germany), and Atreca (San Carlos, CA).
Local Collaboration and WRF Innovation Fellows
The IPD has established tightly woven interdisciplinary collaborations to produce, test and validate new protein designs for vaccines, therapeutics, diagnostics, enzymes, nanomaterials and clean energy. In mid 2014, our collaborative efforts were rewarded with a generous gift from the Washington Research Foundation (WRF) to support our WRF Innovation Fellows program. Over the last few months we have recruited and are supporting 10 talented postdoctoral fellows working on projects 2-3 years in duration where they are applying protein design methods in collaboration with Seattle partner institutes and other UW departments.
Our WRF Innovation Fellows are as follows:
Zachary Crook, James Olson Lab, FredHutch
Computational design of Optides to target blood brain barrier penetration
Jason Gilmore, Michael MacCoss Lab, UW Dept of Genome Sciences
Mass Spectrometry applications for de novo protein design
Benjamin Groves, Georg Seelig Lab, UW Dept of Electrical Engineering
Reengineering protein signaling pathways
Zhizhi Wang, Wenqing Xu Lab, UW Dept of Biological Structure
Developing an inducible protein knockout system for biomedical applications
Yalan Xing, Hannele Ruohola-Baker Lab, UW Dept of Biochemistry/ISCRM
The role of polycomb repressive complex components interaction in the naïve to primed human Embryonic Stem Cell (hESC) epigenetic transition
Gerard Daniel, Thomas Spiro/Karen Goldberg Labs, UW Chemistry
De Novo metalloenzymes with nonbiological metals for in vitro catalysis: Design of (Ru,Zn)-bimetallic active site for photocatalytic reduction of CO2.
Hua Bai, David Galas Lab, Pacific Northwest Diabetes Research Institute
Inhibition of T-cell activation in type 1 diabetes using computationally designed peptides
Hannah Gelman, Douglas Fowler Lab, UW Genome Sciences
Guiding protein design with comprehensive maps of mutant function
Anindya Roy, David Rawlings Lab, Seattle Children’s and UW Immunology
Computational design of B cell maturation antigen (BCMA) binding proteins
Franziska Seeger, Mohamed Oukka, Seattle Children’s
Computational design of high-affinity IL-23 and IL-17 M mimetics: Molecular tools for the treatment of multiple sclerosis and Crohn’s disease
Marc Lajoie, Nora Disis, UW Medicine, Medical Oncology
Design of protein nanorobots to elicit strong T cell response against cancer cells
Recent Scientific Advances
Over the last nine months, our collaborative work at the IPD has been the subject of a number of high-profile research papers that have attracted considerable attention. Two of the papers demonstrate our ability to computationally design proteins that are extremely temperature-stable and with fine-tuned geometries (Huang et al.) and proteins with atomically precise tunable curvatures (Park et al). A collaborative effort between scientists at the IPD and The Scripps Research Institute resulted in a computationally designed protein able to trap enzyme transition states, further improving our abilities to design new enzymes with novel functions (Pearson et al.). In back-to-back papers in Nature Methods, the Baker lab and DiMaio labs describe approaches to determine high-resolution protein structures from lower resolution cryo-electron microscopy (cryo-EM) maps. Cryo-EM is a technique that allows for the observation of proteins in their native environment at extremely low temperatures. The methods described in these papers will significantly improve determination of atomic models from cryo-EM (DiMaio et al., Wang et al.).
Finally, in addition to developing new computational methods and designing new proteins as therapeutics and diagnostic, IPD researchers are working on problems that address environmental and energy storage challenges that we face today. In a recent paper, IPD scientists computationally designed a new enzyme that enables a new route to carbon fixation (Siegel et al.).
Our “War on Ebola”, launched in April 2014, continues to make progress and we have identified computationally designed proteins that bind to the essential glycoprotein coat of several strains of Ebolaviruses, something that no antibody has been able to achieve (See news items below). Our work involving citizen scientists through the Foldit game enabled us to receive a grant from the National Science Foundation to support interactive anti-Ebola protein design with Foldit players.
Our computationally designed anti-Flu virus proteins have been shown to provide both prophylactic and therapeutic protection of rodents from lethal doses of flu viruses (this work is being submitted for publication).
For a broad overview of recent work at the IPD, David Baker’s plenary talk at the AAAS meeting this spring can be viewed at: http://www.aaas.org/annual-meeting/2015/plenaries/post-evolutionary-biology-design-novel-protein-structures-functions-assemblies
New Building in 2016
The IPD is getting too big for its current location, and it is expanding to a new Nanoengineering & Sciences Building being built on the main UW campus this year, to be completed in 2016. The IPD basic research labs, on the 4th Floor of the Molecular Engineering & Sciences, will be expanded into the new space on the 4th Floor of the Nanoengineering & Sciences Building. We are starting a capital campaign to support the build out of the labs and offices for these new IPD facilities.
Thank you
We have experienced a great deal of success, and thanks to your partnership and support, we have much to be proud of. Thank you for sharing our goal of designing a whole new world of synthetic proteins that address 21st century challenges in medicine, energy and technology.
Sincerely,
David Baker, Ph.D.
Professor of Biochemistry, HHMI Investigator, and IPD Director
Recent News
Gamers helping UW in Ebola research – Seattle Times, Aug. 25, 2014
University of Washington taps gamers to tackle Ebola – KOMO TV, Aug. 26, 2014
Foldit Video Gamers Join the Fight Against Ebola Virus – NBC News, Aug. 29, 2014
Can Ebola video game help find a cure for the deadly virus? – Al Jazeera America, Sept. 5, 2014
From donors to research, state has a key role in Ebola fight – Seattle Times, Sept. 18, 2014
Northwest labs and donors leading the fight against Ebola – Seattle Globalist, Sept. 19, 2014
Foldit Reaches 1000 Puzzles, Debuts New Ebola Puzzle – UW CGS, Oct. 21, 2014
Interview with Dr. Frank DiMaio – Biophysical Society TV, Feb.9, 2015
Post-Evolutionary Biology: Design of Novel Protein Structures, Functions, and Assemblies – AAAS 2015 Plenary Lecture by Dr. David Baker, Feb. 14, 2015
UW 360 features celiac disease research of Dr. Ingrid Swanson Pultz – Mar. 19, 2015
UW Researchers developing a cure for celiac disease – KOMO News, May 5, 2015
Publications
IPD researchers are engaged in ~180 different research collaborations with groups in 11 different countries. We publish ~25 research articles each year. Highlighted below are six of the most high profile publications in Science, Nature, and PNAS over the past six months.
Huang P.S. et al. High thermodynamic stability of parametrically designed helical bundles. Science 2014 Oct 24;346(6208):481-5. doi: 10.1126/science.1257481. Epub. Download paper.
Park K. et al. Control of repeat-protein curvature by computational protein design. Nat Struct Mol Biol. 2015 Feb;22(2):167-74. doi: 10.1038/nsmb.2938. Epub. Download paper.
Pearson A.D. et al. Transition states. Trapping a transition state in a computationally designed protein bottle. Science 2015 Feb 20;347(6224):863-7. doi: 10.1126/science.aaa2424. Epub. Download paper.
DiMaio F. et al. Atomic-accuracy models from 4.5-Å cryo-electron microscopy data with density-guided iterative local refinement. Nat Methods 2015 Feb 23. doi: 10.1038/nmeth.3286. Epub. Download paper.
Wang R.Y et al. De novo protein structure determination from near-atomic-resolution cryo-EM maps. Nat Methods. 2015 Apr;12(4):335-8. doi: 10.1038/nmeth.3287. Epub. Download paper.
Siegel J.B. et al. Computational protein design enables a novel one-carbon assimilation pathway. Proc Natl Acad Sci USA 2015 Mar 24;112(12):3704-9. Doi: 10.1073/pnas.1500545112. Epub. Download paper.