When researchers want to study how COVID makes us sick, or what diseases such as Alzheimer’s do to the body, one approach is to look at what’s happening inside individual cells.

Researchers sometimes grow the cells in a 3D scaffold called a “hydrogel.” This network of proteins or molecules mimics the environment the cells would live in inside the body.

New research led by the 天美影视传媒 demonstrates a new class of hydrogels that can form not just outside cells, but also inside of them. The team created these hydrogels from protein building blocks designed using a computer to form a specific structure. These hydrogels exhibited similar mechanical properties both inside and outside of cells, providing researchers with a new tool to group proteins together inside of cells.

The team Jan. 30 in the Proceedings of the National Academy of Sciences.

“In the past 10 years, there’s been a shift in the world of cell biology,” said co-senior author , a UW associate professor of chemical engineering and of bioengineering. “Classically, folks have attributed much of the cell鈥檚 interior organization to membrane-bound organelles, such as mitochondria or the nucleus. But now scientists are realizing that the cell actually has other ways to locally concentrate certain molecules or proteins without using membranes, for example, by protein-protein interactions. This concentrating allows the cell to turn on or off specific functions that can be helpful or ultimately lead to disease.”

DeForest continued: “What I think is pretty exciting here is that we have good mechanical control of our hydrogels 鈥� even when they are made inside human cells. This means we can tune them to essentially function as a synthetic version of whatever sequestering phenomenon we want to study, such as how protein aggregation can lead to Alzheimer’s.”

One key element of this research was that the protein building blocks were designed from scratch 鈥� they don’t exist anywhere in nature 鈥� using computers.

“You can imagine a protein as a string of subunits called amino acids. That string folds up to form a three-dimensional structure. There are 20 different amino acids, and a typical protein is made up of 100 to 200 of them. That makes the system very complex, because how do you know how it’s going to fold?” said co-lead author , who completed this research as a UW postdoctoral researcher at the and is now a research fellow at Harvard Medical School and Boston Children’s Hospital. “That’s where the computer comes into play 鈥� it does calculations to estimate the most likely three-dimensional shape. And similarly, you can tell it what shape you want and it tells you what sequence you need to build the protein.”

To make a variety of hydrogels with different properties, the team used computational design to control how floppy or rigid the protein building blocks were and how the building blocks organized and connected to create the hydrogel. The researchers also used two different methods to link the building blocks together: One linked them irreversibly and the other allowed the proteins to disconnect and reconnect.

“Irreversibly crosslinked systems are going to be intrinsically more stable, making them better for long-term cell culture and functional tissue engineering,” said DeForest, who is also a faculty member with the UW and the UW . “But the reversibly crosslinked systems are more fluid, which may be better for driving specific protein-protein interactions within living cells.”

To determine if the hydrogels in cells had similar characteristics compared to their extracellular counterparts, the researchers examined whether building blocks within the hydrogels could move around. A stiffer hydrogel would be more likely to trap the proteins in one position compared to a more fluid gel. The mechanical properties of each type of hydrogel remained even when inside a cell.

The team plans to further explore this system, including being able to better control how hydrogels form and localize within cells.

The most crucial part of this project, the researchers said, was the collaboration between protein designers and chemical and biological engineers.

“Our cross-disciplinary collaboration with Cole鈥檚 group has been very exciting, and has opened up routes to new classes of biomaterials with a wide range of applications,” said co-senior author , the director of the Institute for Protein Design and a professor of biochemistry in the UW School of Medicine.

, a UW doctoral student in bioengineering, is co-lead author on this paper. Additional co-authors are , a UW research scientist in the Institute for Protein Design; , an assistant professor at Pohang University of Science and Technology who completed this research as a UW postdoc at the Institute for Protein Design; , a UW doctoral student in bioengineering; , a UW doctoral student in molecular and cellular biology; , a UW doctoral student in biological physics, structure and design; , a UW research scientist at the Institute for Protein Design; , a group leader at the Hubrecht Institute who completed this research as a postdoc at the Institute for Protein Design; , an acting instructor at the Institute for Protein Design; Alee Sharma, an undergraduate student at Northeastern University; and , an associate professor at the Johns Hopkins School of Engineering. Mout and Sahtoe were part of the . This research was funded by the National Science Foundation, the Audacious Project, the Open Philanthropy Project, the Wu Tsai Translational Investigator Fund, the Center for the Science of Synthesis Across Scales and the National Institutes of Health.

For more information, contact DeForest at profcole@uw.edu, Mout at rubul.mout@childrens.harvard.edu and Baker at dabaker@uw.edu.

The 天美影视传媒 is proud to announce that more than 40 faculty and researchers who completed their work while at UW have been named on the annual list from Clarivate.

The annual list identifies researchers who demonstrated significant influence in their chosen field or fields through the publication of multiple highly cited papers during the last decade. Their names are drawn from the publications that rank in the top 1% by citations for field and publication year in the Web of Science citation index.

The list of faculty and researchers whose primary affiliation is with the UW or with the Institute for Health Metrics and Evaluation who were acknowledged for their work includes:

David Baker

William A. Banks

Gregory N. Bratman

Steven L. Brunton

Guozhong Cao

William A. Catterall

Helen Chu

David H. Cobden

Katharine H.D. Crawford

Riza M. Daza

Frank DiMaio

Evan E. Eichler

Michael Gale Jr.

Raphael Gottardo

Allison J. Greaney

Alexander L. Greninger

Simon I. Hay

Celestia S. Higano

Neil P. King

James B. Leverenz

Charles M. Marcus

Philip Mease

Ali Mokdad

Thomas J. Montine*

Christopher J. L. Murray

Mohsen Naghavi

William S. Noble

Young-Jun Park

David M. Pigott

Stanley Riddell

Andrea Schietinger **

Jay Shendure

M. Alejandra Tortorici

Troy R. Torgerson***

Cole Trapnell

David Veesler

Theo Vos

Alexandra C. Walls****

Bryan J. Weiner

Spencer A. Wood

Sanfeng Wu

Di Xiao

Xiaodong Xu

The that determines the 鈥渨ho鈥檚 who鈥� of influential researchers draws on the data and analysis performed by bibliometric experts and data scientists at the Institute for Scientific Information at Clarivate. It also uses the tallies to identify the countries and research institutions where these scientific elite are based.

The full 2023 Highly Cited Researchers list and executive summary can be found online .

* now is at Stanford University.

** now is at Memorial Sloan Kettering Cancer Center.

*** now is at the Allen Institute.

**** now is at BoiNTech SE.

now is at Princeton University.

The 天美影视传媒 Board of Regents last week approved the development plan for the first major project in the 鲍奥鈥檚 newly named Portage Bay Crossing area on the west side of the Seattle campus. The Regents approved a ground lease of the property at Site W27 to Wexford Science + Technology and a lease of building space by the University.

鈥淭his is a significant milestone for the UW and we are so excited to expand into the area west of campus and begin to define Portage Bay Crossing as a new place for discovery and innovation,鈥� said Lou Cariello, the 鲍奥鈥檚 vice president for facilities. 鈥淲e envision this as a lively and vibrant place with a mix of academic, arts, culture and retail spaces where students, researchers and others can engage in support of the 鲍奥鈥檚 learning, research, health care and public service missions.鈥�

Wexford will develop and manage long-term an 11-story building totaling about 340,000 rentable square feet of lab, office, collaboration and retail space. The 鲍奥鈥檚 Clean Energy Institute, Brotman Baty Institute and Institute for Protein Design are slated to occupy a significant amount of the space.

鈥淭he Clean Energy Institute is excited to have the Regents approve this project in Portage Bay Crossing,鈥� said Daniel Schwartz, director of the Clean Energy Institute and professor of chemical engineering. 鈥淚n recent years, the Washington Clean Energy Testbeds have attracted about 600 facility users from the UW and other research organizations across the state and nation who work side by side with a group of roughly 60 companies.聽The dynamic environment in this new space will unleash Washington students, faculty and companies to create home-grown technologies that can scale solutions to address the climate crisis.鈥�

The sits just south of NE 40th Street and is bounded by University Way NE to the east, Brooklyn Avenue NE to the west, and the Burke-Gilman Trail and NE Pacific Street to the south.

鈥淭his is a momentous opportunity for two of UW Medicine鈥檚 significant and thriving institutes,鈥� said Ruth Mahan, chief business officer and chief of staff at UW Medicine and the 鲍奥鈥檚 vice president for medical affairs. 鈥淧lacing the Brotman Baty Institute and the Institute for Protein Design in one location will provide each with space to grow, enhance collaborations between them and accelerate translation of discoveries into effective treatments.鈥�

The vision for Portage Bay Crossing is to create a place where student and faculty experts across multiple fields 鈥� including public health, engineering, life sciences, social work, public policy, the humanities, physical sciences and environmental studies 鈥� can partner with business, government, nonprofit organizations and the Seattle community to solve critical challenges.

# # #

For more information, contact Victor Balta at balta@uw.edu.

Four 天美影视传媒 professors were among the winners of the 2021 Breakthrough Prize, which recognizes groundbreaking achievements in the life sciences, fundamental physics and mathematics.

David Baker, a professor in the UW School of Medicine鈥檚 department of biochemistry, won the prize for life sciences, while a team of UW physics professors, including Eric Adelberger, Jens Gundlach and Blayne Heckel, earned the prize for fundamental physics.

The annually awards the Breakthrough Prizes, which were founded in 2013 and are dubbed the 鈥淥scars of Science.鈥� Each prize is worth $3 million.

Baker, director of the , was recognized for developing technology that allowed the design of proteins never seen before in nature, including novel proteins that have the potential for therapeutic intervention in human diseases.

Over billions of years, nature has produced a thousand trillion proteins聽鈥� the workhorse molecules essential to every life function聽鈥� each with a unique origami-style design that allows it to precisely lock onto an adjacent molecule to perform its unique function. Then came the Protein Design Revolution, harnessing supercomputing and newly discovered principles of how natural proteins fold to turn evolution on its head.

鈥淲e could wait another million years for the protein we need to evolve, or we could design it ourselves,鈥� Baker said. His enthusiastic design community of 250,000聽鈥� citizen scientists, Foldit players and gamers聽鈥� uses a combination of human ingenuity and automated computational firepower. Their latest project is a promising crowd-sourced novel protein that could adhere to a COVID-19 virus and destroy it.

鈥淥ne-hundred people will approach the solution to a problem from 100 different perspectives,鈥� said Baker, who invented the open-source Rosetta software for computational modeling and analysis of novel proteins. The promise of protein design? Universal vaccines for flu, HIV, COVID-19 and cancer; medicines for chronic pain; smart therapeutics; nanoengineering for solar energy capture, and more.

鈥淚 am excited about this award accelerating progress at the IPD in de novo design of new proteins not found in nature to address current challenges in medicine and beyond,鈥� Baker said. 鈥淚 thank my wonderful colleagues聽鈥� undergraduate and graduate students, postdocs, faculty and staff聽鈥� at the IPD and UW, and members of the general public contributing to our efforts through the rosetta@home and Foldit projects.鈥�

The award gives Baker and Gundlach, longtime friends who go on hikes and climbs together, something new to talk about the next time they hit the trails.

鈥淒avid is very well deserving of this prize,鈥� said Gundlach, who currently serves as principal investigator on the 鈥檚 research in physics. 鈥淗e has really pioneered the field of protein folding in a major way.鈥�

The E枚t-Wash Group, made up of UW physicists Adelberger, Gundlach and Heckel, was recognized for precision fundamental measurements that test our understanding of gravity, probe the nature of dark energy and establish limits on couplings to dark matter is.

“I think the award was quite unexpected to all of us, but as a surprise it generates even more joy,鈥� Gundlach said. 鈥淧resenting our research to the public was always rewarding because our experiments are intriguing and fun to hear about, but knowing that a panel of famous physicists selected our work feels particularly rewarding.鈥�

The equivalence principle 鈥� the observation that objects, whatever they are made of, fall with the聽same acceleration 鈥� inspired Albert Einstein’s聽relativistic theory of gravity. Motivated by the unexplained phenomena of聽dark matter and dark energy that hint towards new physics, as well as theoretical attempts to develop unified quantum theories of gravity that聽inherently predict violations of the equivalence principle and additional curled-up space dimensions,听the UW E枚t-Wash team decided to probe the fundamental properties of gravity with a new generation of instruments.

They took the two-century-old torsion balance concept and developed it into a supremely sensitive 21st-century instrument to look for new fundamental physics. They tested the equivalence principle, the inverse square law, and measured the gravitational constant聽with unprecedented precision and sensitivity.聽For example, their latest inverse-square law test probed gravity at ultra-short distances, establishing that any extra dimension must be curled up with a radius less than one-third聽the diameter of a human hair.

Last year, Lukasz Fidkowski, an assistant professor of physics at the UW, won the New Horizons in Physics Prize from the Breakthrough Foundation. At least three researchers associated with the UW have received Breakthrough prizes in prior years.

Each year, the Prize is celebrated at a gala award ceremony, where the awards are presented by superstars of movies, music, sports and tech entrepreneurship. Due to the COVID-19 pandemic, however, this year鈥檚 ceremony has been postponed until March 2021.

For more information, contact Victor Balta at balta@uw.edu.

David Baker, Dayong Gao, Herbert Sauro named fellows of the American Institute for Medical and Biological Engineering

UW professors , and have been named fellows of the .

The three faculty members are among the institute’s , numbering 157 in all, chosen for their “distinguished and continuing achievements” in medical and biological engineering.

Called the AIMBE for short, the institute is a Washington, D.C.-based nonprofit organization. Its 2,000-member College of Fellows includes outstanding engineers, entrepreneurs and innovators in medical and biological engineering.

The organization advocates for the value of medical bioengineering in society. Its mission, which also drives advocacy initiatives, is to “recognize excellence, advance the public understanding and accelerate medical and biological innovation,” according to its website.

Baker is a professor of biochemistry and directs the . Gao is a professor of mechanical engineering and director of the . Sauro is a professor of bioengineering and director of the . All three have affiliate appointments in other departments as well.

Election to the institute’s College of Fellows is among the highest professional distinctions accorded to a medical and biological engineer; fellows include three Nobel Prize laureates and 18 recipients of the Presidential Medal of Science or National Medal of Technology and Innovation. The institute’s annual meeting, scheduled for March, was cancelled due to health concerns and the fellows were inducted remotely.

***

Essay fondly remembers Ellis Goldberg, professor of political science

A researcher with the nonprofit has penned a remembrance and appreciation of , UW professor of political science, who September 20, 2019, at the age of 72.

Goldberg, a political economist and scholar of Middle East politics, was a longtime UW faculty member and former director of the Middle East Center in the Jackson School of International Studies. He also wrote a blog called “” that commented on Middle Eastern and U.S. politics.

He is remembered fondly on the Middle East research project’s website by , clinical assistant professor in Liberal Studies at New York University, in an essay titled “Ellis Goldberg, Egypt and a Reverence for Life.”

El-Ghobashy writes that Goldberg “loved Egypt and knew more about its history and political economy than anyone I know. 鈥� At a time when lives in Egypt are imperiled by deprivation, dictatorship and disease, as are so many lives across the globe, an intellectual sensibility grounded in a reverence for life is a gift and an exigency.”

With Goldberg’s death, El-Ghobashy writes, “we lost one of the most erudite, generous and original scholars of the modern Middle East and North Africa, a truly reflective mind 鈥�”聽 .

There were remembrances of Goldberg from the and the as well.

UW Notebook is a section of the UW News site dedicated to telling stories of the good work done by faculty and staff at the 天美影视传媒. Read all posts here.

With $4 million in matching funds from the National Institutes of Health, the 天美影视传媒 has created a new integrated center to match biomedical discoveries with the resources needed to bring innovative products to the public and improve health.

鈥淭he 天美影视传媒 and regional partner institutions produce some of the most exciting biomedical discoveries and technologies in the world, but we always find it challenging to support their product development as they move into the early commercialization phases,鈥� said the new center鈥檚 executive director聽, a professor in the UW School of Pharmacy.

With well over a billion dollars in聽research funding聽annually, the 天美影视传媒 is an engine of discovery and generates more than聽$15 billion聽in the state鈥檚 economy.

鲍奥鈥檚 newly funded Washington Entrepreneurial Research Evaluation and Commercialization Hub (WE-REACH), with an annual budget boosted to $1.4 million by contributions from other partners, is organized to mentor and support biomedical entrepreneurs as well as provide project funding to fuel four to six biomedical startups a year with up to $200,000 each.

Those projects will include innovative disease treatments, new drugs, diagnostics, genetic testing and health technologies. Ho said the center will support innovation steps not typically supported by research grants, such as human clinical trials or the development of and access to products.

In addition to the NIH, WE-REACH partners include the UW聽,听, the聽聽and the聽. Innovators will receive guidance from multiple academic departments and regional institutions. Those institutions include the Fred Hutchinson Cancer Research Institute, Seattle Children鈥檚 and other universities in the five states that make up the聽听谤别驳颈辞苍.

鈥淲e are delighted to welcome WE-REACH as a partner,鈥� said聽, executive director of the Institute of Translational Health Sciences.聽鈥淎t ITHS we are committed to accelerating the translation of discoveries to the clinic. WE-REACH investigators will be able to leverage ITHS programs and resources, so they can help us in our mission to improve health in our communities. This is a very exciting area of translation that we are happy to support.鈥�

WE-REACH is one of five national commercialization聽聽selected for funding by the NIH in 2019.

鈥淭he journey of biomedical discoveries to products that improve people鈥檚 health is expensive and risky. The process requires strategic investment of know-how as well as financial support from public-private partnerships,鈥� said Ho.

鈥淪pinning life science innovations out of research institutions requires expertise and funding that is hard to source in the academic environment,鈥� adds聽, assistant vice president, innovation development at CoMotion, 鲍奥鈥檚 collaborative innovation hub. 鈥淲E-REACH builds on the infrastructure CoMotion has developed, including our gap fund and training, to provide critical resources needed to de-risk promising technologies into preclinical and clinical development.鈥�

The new center will be located in the South Campus Center on the 天美影视传媒鈥檚 Seattle campus and at the Institute of Translational Health Sciences in UW Medicine South Lake Union. It will be staffed by Professor Rodney Ho, Executive Director; Terri Butler, Associate Director of Outreach and Partnerships; Matthew Hartman, Coordinator; Christine Jonsson, Administrator; and new hires in project management and technology management roles.

For information on the new center and how to submit a grant proposal,听please contact Matthew Hartman at聽WEREACH@uw.edu聽or 561-339-0676.聽The next round of grant funding requires a declaration of intent by Feb. 7 and complete submission by May 1.

NIH Grant: 1 U01 HL152401-01

Learn more about the 鲍奥鈥檚 Population Health Initiative: a 25-year, interdisciplinary effort to bring understanding and solutions to the biggest challenges facing communities.

The United States Department of Energy has awarded an expected $10.75 million, four-year grant to the 天美影视传媒, the and other partner institutions for a new interdisciplinary research center to define the enigmatic rules that govern how molecular-scale building blocks assemble into ordered structures 鈥� and give rise to complex hierarchical materials.

The Center for the Science of Synthesis Across Scales, or CSSAS, will bring together researchers from biology, engineering and the physical sciences to uncover new insights into how molecular interactions control assembly and apply these principles toward creating new materials with novel and revolutionary properties for applications in energy technology.

“This center seeks to understand the fundamental rules of how order emerges from the interaction of simple building blocks,” said CSSAS Director , the Matthaei Professor and Chair of the UW Department of Chemical Engineering. “What are the energetics, rates and pathways involved, and what properties emerge when simple components come together in increasingly complex layers? Those are some of our driving questions.”

The UW-based CSSAS is among the newest members of the Energy Frontier Research Centers by the Department of Energy. These centers, operated out of universities and national labs, are funded by the Department of Energy and devoted to specific goals in energy science. The work at the CSSAS will focus on understanding the principles of “hierarchical synthesis” 鈥� the process by which molecules come together, bind, interact and create layer upon layer of higher-ordered structures.

CSSAS experiments will focus on protein-based building blocks, but will also probe protein-like synthetic compounds called peptoids as well as inorganic nanoparticles. Studying the biologically inspired assembly of these systems individually and in combination will shed new light on how living organisms, through billions of years of adaptation and evolution, have created complex hierarchical systems to solve a host of challenges, said Baneyx.

Understanding hierarchical synthesis would allow engineers to design and build new materials with unique properties for innovative technological advancements that can come about only when scientists exert precise control over a material. For example, controlling how charges move precisely through a material 鈥� or how a substrate is shuttled between the active sites of a series of enzymes positioned with nanoscale precision 鈥� could be key to creating new materials for energy storage, transmission and generation. The precision control that scientists envision could also yield functional materials that are self-healing or self-repairing, and have other custom physical properties designed within them.

“Scientists have been trying to create these types of innovative materials largely through ‘top-down’ approaches, and often by reverse engineering an interesting biological material,” said Baneyx. “We will begin with the blocks themselves, exploring how order evolves in the synthesis process when the blocks are put together and interact.”

CSSAS research will focus on three major areas:

• Investigating the emergence of order from the interactions of individual building blocks, be they peptoids, inorganic nanoparticles or protein-based particles
• Probing how hierarchy unfolds as these building blocks are combined to construct lattices, active structures and hybrid materials
• Using machine learning, computational simulations and big data analytics to learn new ways to control the assembly dynamics of hierarchical structures

These investigations will build upon work conducted at the UW , led by UW biochemistry professor and Howard Hughes Medical Institute investigator , and harness the expertise of researchers at the University of Chicago, the Oak Ridge National Laboratory and the University of California, San Diego.

The CSSAS effort was enabled by , or NW IMPACT, which was formally launched earlier this year by UW President Ana Mari Cauce and PNNL Director Steven Ashby to fertilize cross-disciplinary collaborations between UW and PNNL researchers. NW IMPACT co-director , who is the PNNL chief scientist for materials synthesis and simulation across scales and also holds a joint appointment at the UW in both chemistry and materials science and engineering, will serve as the deputy director of the CSSAS.

“This center’s focus is ultimately on unlocking potential,” said Baneyx. “Once we understand the fundamental rules governing the assembly of bioinspired building blocks, we will be able to design new materials to meet a broad range of technological needs.”

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For more information, contact Baneyx at 206-685-7659 or baneyx@uw.edu and De Yoreo at 509-375-6494 or james.deyoreo@pnnl.gov.

The award will fund four interdisciplinary initiatives that seek to advance global innovation in clean energy, protein design, big data science and neuroengineering.

The funding will be used to hire new faculty, attract competitive postdoctoral researchers and enhance facilities and infrastructure. The goal is to boost the UW’s contribution in these high-need research areas and encourage spinout companies among involved researchers.

“This is a watershed moment for the university and Washington Research Foundation,” said UW President Michael K. Young.聽“To see investors in Washington supporting their flagship research university makes a strong statement about how important such local investment is. The four grant recipient groups include some of our most productive and creative faculty, and we are deeply grateful to the foundation for its vote of confidence in their work.”

The award, given to four projects over six years, represents the largest gift by the foundation to the UW. The funding is unusually flexible, allowing each project team to name specific resources it needs to meet its stated goals, said , UW vice provost for research and a professor of chemical engineering and microbiology.

“The projects impact a large number of departments in multiple schools and colleges, resulting in a broad and sustained impact for the university as a whole,” Lidstrom said. “This investment will also have long-lasting economic impact to the larger community, creating jobs and revenue in high-tech areas for many years to come.”

The projects were chosen based on the researchers who lead them and their competitive positions in their respective fields, as well as the possibility the UW research will set a global standard and create the clear potential for spinout companies. University leaders worked with the foundation to identify an initial group of six projects, and after reviewing proposals and visiting with each group the foundation selected four to fund.

“We’re very pleased to continue and solidify our long-term relationship with the 天美影视传媒,” said Ronald Howell, president and CEO of Washington Research Foundation. “And聽our strategic investment will help the UW recruit and retain the very best people who can advance scientific discovery. Hopefully, this will pave the way for greater innovation in data analysis,听neuroengineering, protein design and clean energy as we move into the future.”

The foundation is a nonprofit organization that supports cutting-edge research and early stage entrepreneurs in the areas of life sciences, information technology and physical sciences. It also seeks to help grow Washington’s technology economy.

The four UW projects funded by Washington Research Foundation are:

Institute for Protein Design Innovation Fellows
$8 million over six years

The will recruit and hire about 12 scientists to be based at Seattle-area labs that collaborate with the UW institute and specialize in the fields of health, medicine, computer science, materials science and engineering.

The scientists, or innovation fellows, will work at various collaborating organizations, but will be trained in protein design at the UW. They will apply the methods they learn to help solve current research challenges while at their host organizations. The goal is to recruit top-notch scientists who have the potential to become tenure-track professors.

The Institute for Protein Design formed in 2012 with the mission to design new synthetic proteins that address current challenges in medicine, energy and technology. Gov. Jay Inslee and the state Legislature provided $1 million in funding in the 2014 supplemental budget to support the institute.

from the Institute for Protein Design.

Institute for Neuroengineering
$7.19 million over six years

A number of UW schools, colleges and departments will use the award to establish an Institute for Neuroengineering, which will foster collaborative research across many disciplines to address current challenges in neural disorders and functions, and provide new technologies for people affected by neural disorders.

The team plans to hire two junior-level faculty members in the areas of sensory information processing and computational neuroscience.

The funding will also support nine postdoctoral researchers, nine graduate students, nine undergraduate students and nine high school student interns. In addition, it will support building renovations in the Department of Biology to house new research. Research will take place jointly with the at the UW.

Global Leadership in Data-Intensive Discovery
$9.27 million over six years

Rapid advances in technology are transforming nearly every field from “data-poor” to “data-rich” 鈥� not only in the sciences, engineering, and medicine, but also in the social sciences and increasingly in the humanities. The ability to extract knowledge from this abundance of data is important for breakthroughs in research.

This team, which includes 13 faculty members spanning nine departments and four schools and colleges, is working to ensure that the UW is a leader both in advancing the methodologies of data science and in putting these advances to work in many different fields.

Operating under the umbrella of the UW’s , the team will hire six new faculty members specializing in methods and applications of big data, establish three chairs and three professorships and recruit 13 postdoctoral researchers.

Funding will also support the remodel of space on campus to house the UW’s new “data science studio,” an area where data scientists and researchers across fields can work collaboratively on projects.

Excellence in Clean Energy Innovation
$6.74 million over six years

The UW’s will hire nine new faculty members who will focus on lowering the cost and increasing the performance of solar energy production, storage and delivery. Research will include the discovery of advanced materials for solar cells and batteries, manufacturing methods that are lower cost, and the development of new software and hardware strategies for integrating clean energy with systems and the grid.

The funding will also support six new postdoctoral researchers and the creation of a new experimental manufacturing facility on campus that will help move discoveries from the laboratory to the marketplace.

The Legislature and Inslee established the institute in 2013 to be a research center for advancing solar energy and electrical energy storage capabilities.

from the Clean Energy Institute.

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For more information:
天美影视传媒: Mary Lidstrom: lidstrom@uw.edu or 206-685-7641.
Washington Research Foundation: Steven Gottlieb: s.gottlieb@greenc3.com or 206-427-9591.

Project contacts:

Institute for Protein Design Innovation Fellows
, senior director of strategy:聽ljs5@uw.edu聽or 206-616-7542.

Institute for Neuroengineering
, professor of biology:聽danielt@uw.edu聽or 206-543-1659.
, associate professor of physiology and biophysics:聽fairhall@uw.edu聽or 206-427-1557.

Global Leadership in Data-Intensive Discovery
, professor of computer science and engineering:聽lazowska@cs.washington.edu聽or 206-543-4755.

Excellence in Clean Energy Innovation
, professor of chemical engineering: uwcei@uw.edu or 206-685-6833.

The achievement could have far wider ranging applications in medicine and other fields, according to the Protein Design Institute at the 天美影视传媒.

鈥淭his is major step toward building proteins for use as biosensors or molecular sponges, or in synthetic biology — giving organisms new tools to perform a task,鈥� said one of the lead researchers, Christine E. Tinberg, a postdoctoral fellow in biochemistry at the UW.

The approach they took appears in the Sept. 4 online issue of Nature. Tinberg and Sagar D. Khare headed the study under the direction of David Baker, UW professor of biochemistry and Howard Hughes Medical Institute investigator. Khare is currently an assistant professor at Rutgers University.

Their is accompanied by a News & Views “Computational biology: A recipe for ligand binding proteins.” The commentator, Giovanna Ghirlanda of Arizona State University, wrote that the method developed “to design聽 proteins with desired recognition sites could聽 be revolutionary” because cell processes such as cell cross-talk, the production of gene products and the work of enzymes all depend on molecular recognition.

The scientific team overcame previously unsolved problems in building accurate protein-small molecule interfaces.聽 Earlier attempts struggled with discrepancies between the computer plans and the structures of the actual molecules.

In conducting the study, the researchers learned general principles for engineering small molecule-binding proteins with strong attraction energies. Their findings open up the possibility that binding proteins could be created for many medical, industrial and environmental uses.

In medical diagnostics, for example, a rationally programmed protein might detect biomolecules found only in a specific disease state, such as an early-stage cancer.聽 Other types of protein molecules might eventually be manufactured to treat an overdose or to block a poison. Remediation possibilities for these molecular workhorses could include trapping pollutants or capturing waste.

Tinberg explained that generation of novel small-molecule binding proteins currently consists of immunizing an animal to generate antibodies against a target protein, or directing the evolution of proteins in a laboratory to strengthen their affinity for the desired small-molecule.

鈥淣either of these methods allows complete control over the interactions involved in binding,鈥� she said.

In designing their molecules, the team sought to replicate properties of a naturally occurring protein binding site. These are: specific interactions that enforce a strong attraction with the desired small molecule, a receptive shape to accept the small molecule, and an orderly structure, prepared for occupancy. The exclusive, move-in ready set up reduces the energy penalty by preventing the protein from having to change shape to accept the small molecule.聽 This is in contrast to a flexible site, which is more disordered in the absence of the small molecule and has to freeze into one state upon binding.

The scientists programmed the necessary protein-molecule interactions 鈥� and generated additional buttresses 鈥� mainly through the conformation and orientation of the binding site architecture.

鈥淥ur goal was a snug fit,鈥� Tinberg said.

The researchers adapted a computational tool called Rosetta developed in the Baker lab to craft new proteins that would bind the steroid digoxigenin, which is related to the heart-disease medication digoxin. The drug can cause digestive problems, confusion, vision disturbances and heart beat irregularities. 聽The difference between a helpful and a harmful dose is slight. At present patients receive antibodies directed at the molecule to correct excess amounts.

After generating many designs for digoxigenin-binders on a computer, the researchers chose 17 to synthesize in a lab. Experimental tests led the researchers to hone in on the protein they called DIG10.聽 Further observations revealed that the binding activities of this protein were indeed mediated by its computer-designed interface, just as the researchers had intended.

To upgrade their overall design methods, the researchers then used next-generation deep gene sequencing to probe the effect of each amino acid molecular building block on binding fitness. Using this method, they were able to discover how various engineered genetic variations affect the designed protein鈥檚 binding capabilities.聽 The binding fitness map gave the researchers ideas for enhancing the binding affinity of the designed protein to the picomolar level, tighter than the nano-level.

The scientific team waited eagerly for the X-ray crystallography 鈥� a way of taking a picture of a molecule. It showed that the actual structures of two protein molecules matched at the atomic level with the computer-generated designs.

No longer did the researchers have to contend with the supposedly insurmountable roadblock 鈥� the mismatches between the design model and the protein generated in the lab.

Another goal of the work was to ensure that the designed proteins bound the small molecule target and not chemically related molecules. This mistaken link-up could lead to side effects if the protein were used as a therapeutic. The researchers were pleased when their protein selected digoxigenin over three related steroids.

The scientists went on to redesign parts of the binding interface to change the protein molecule鈥檚 preferences among three related steroids.聽 The molecule could be reprogrammed to select either digitoxigenin (a relative of digoxin), progesterone (a female hormone), or B-estradiol (an estrogen-replacement drug.).聽 The scientists manipulated the molecule鈥檚 choices by altering its hydrogen bonding interactions.

The crystal structures of two designed proteins bound to digoxigenin have been deposited in the RCSB Protein Data Bank.

鈥淏y continually improving the methodology and with feedback from experimental results,鈥� the researchers noted in their paper, 鈥渃omputational protein design should provide an increasingly powerful approach to creating small molecule receptors for synthetic biology, therapeutic scavengers for toxic compounds, and robust binding domains for diagnostic devices.鈥�

The study, 鈥淐omputational Design of Ligand Binding Proteins with High Affinity and Selectivity鈥� was supported by grants from the U.S. 聽Defense Threat Reduction Agency and the Defense Advanced Research Projects Agency (DARPA), the Swiss National Science Foundation, and National Science Foundation Grant MCB 1121896.

In addition to Tinberg, Khare and Baker, the other scientists on this project were Jiayi Dou of the UW Department of Bioengineering and the graduate program in Biological Physicians, Structure and Design; Lindsey Doyle and Barry Stoddard of the Division of Basic Sciences at Fred Hutchinson Cancer Research Center in Seattle; Jorgen W. Nelson of the UW Department of Genome Scientists, Alberto Schena and Kai Johnsson of the National Centre of Competence in Research in Chemical Biology in Lausanne, Switzerland;聽 and Wojciech Jankowski and Charalampos G. Kalodimos of Rutgers University.