Recent work by Jesse Zalatan featured on the cover of Cell

Assistant Professor Jesse Zalatan and co-workers at the UCSF have developed a method to encode complex, synthetic transcriptional regulatory programs using the CRISPR-Cas system. Natural biological systems can switch between different functional or developmental states depending on the particular set of genes being expressed, and the ability to synthetically control gene expression has important implications as both a research tool and as a means to engineer novel cell-based therapeutics and devices.

Zalatan and coworkers designed CRISPR-Cas RNA scaffold molecules that specify both a DNA target and the function to execute at the target, so that sets of RNA scaffolds can be used to generate a synthetic, multigene transcriptional program in eukaryotic cells in which some genes are activated and others are repressed. These types of programs can be used to reprogram complex reaction networks in biological systems, such as metabolic pathways or signaling cascades.

For more information about Professor Zalatan and his research, please visit his faculty page and research group website.

Boydston research group has back-to-back papers highlighted in C&E News

boydstonResearch by Assistant Professor AJ Boydston and his group has been featured in two recent articles in the American Chemical Society’s Chemical & Engineering News. An article in the December 18, 2014 issue highlights his research on polymers that change color when stretched (http://cen.acs.org/articles/92/web/2014/12/3-D-Printed-Polymer-Devices.html). Just one month later, an article in the January 19, 2015 issue summarized the Boydston group’s research on a metal-free route to prepare polymers (http://cen.acs.org/articles/93/i3/Radical-Polymer-Approach.html).

For more information about Professor Boydston and his research program, please visit his faculty page and research group website.

UW researchers uncover the molecular basis of the heartbeat

Stoll HCNconformationchange editAssistant Professor Stefan Stoll (Chemistry), Professor William Zagotta (Physiology & Biophysics), and co-workers have used double electron-electron resonance (DEER) spectroscopy to determine the structural origins of the regulatory function of cyclic adenosine monophosphate (cAMP) on an important ion channel. Their work reveals that binding of the cAMP induces a large structural change in the intracellular part of the channel. The ion channel studied, a hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channel, is critical to the function of heart, as it is part of the heart’s natural pacemaker. The HCN channel is crucial in regulating the heartbeat: binding of cAMP to HCN increases of the heart rate. This work, reported in the Proceedings of the National Academy of Sciences, could form the basis for better drug design for disorders of electrical signaling in the heart. (A movie showing a model of the structural change can be downloaded in Quicktime format from: http://felix.chem.washington.edu/HCN_DEER_movie.mov.)

To learn more about Professor Stoll and his research, please visit his faculty page and research group website.

To learn more about Professor Zagotta and his research, please visit his faculty page.

Department ranks 10th nationally for research spending

nsf_smallOne measure of the scale and strength of chemistry research programs is success in the allocation of competitively awarded grant and contract funds in support of research. The Department of Chemistry at the University of Washington has in recent years been among the leaders nationally by this measure. According to the most recent (2012) National Science Foundation Survey of Higher Education Research and Development, the University of Washington Department of Chemistry is ranked 10th nationally for overall research and development spending in chemistry, appearing just below the Department of Chemistry at the Massachusetts Institute of Technology for total expenditures. In terms of federally-funded research and development spending, the Department of Chemistry ranks 8th nationally.

Date related to the survey can be found at http://www.nsf.gov/statistics/herd/.

Multi-disciplinary approach to understanding Botulinum toxin

RonetalFigResearch Associate Professor Werner Kaminsky contributed to a research project recently highlighted in Nature. With the catch phrase “BOTOX paralyses zebrafish muscles and blocks fin regeneration”, Nature highlighted a publication on the effect of Botulinum toxin on bone regeneration,[i] tested on small fish, whose fins were cut-off (under sedation), then regrown while testing different amounts of medications administrated to the fish’s dorsolateral trunk and the base of the tail fin prior to surgery.[ii] Nature summed up the findings with “muscle paralysis (was) similar to that seen in mammals and humans in that it was focal, dose-dependent and short-lasting.” and “BTx treatment had a negative impact on bone formation during fin regeneration.” The work involved a truly diverse multi-discipline co-operation between members of three departments on the UW campus: Orthopaedics and Sports Medicine, Pharmacology, and Chemistry. The regenerating zebrafish tail fin often provides a compelling model for therapeutic studies. However, a major hurdle to such efforts is the lack of quantitative modalities for bone mineralization analysis. Kaminsky contributed his patented microscopy technology to determine bone mineralization with a custom built automated polarized light microscope to sequentially acquire images under a stepwise rotating polarizer. This enabled birefringence to be decoupled from transmittance and orientation, allowing for quantitative analysis.

 

[i]http://onlinelibrary.wiley.com/doi/10.1002/jbmr.2274/abstract;jsessionid=DF9492DBD18E5943C72A2F63D73A2816.f03t04

[ii]http://www.nature.com/bonekey/knowledgeenvironment/2014/140806/bonekey201463/full/bonekey201463.html

Clean Energy Institute Launches

CleanEnergyInstKickoff_sqA new University of Washington institute to develop efficient, cost-effective solar power and better energy storage systems launched December 12 with an event attended by UW President Michael K. Young, Gov. Jay Inslee and researchers, industry experts and policy leaders in renewable energy.

The Clean Energy Institute formed when Washington’s governor and state legislators last summer allocated $6 million to create a research center at the university that will advance solar energy and electrical energy storage capacities. The institute will better connect and boost existing energy research at the UW as well as attract new partnerships and talent, including new faculty members.

The opening of the Clean Energy Institute was covered by KIRO 7 News, the Seattle Times, and UW News. Chemistry Professor David Ginger, Raymon E. and Rosellen M. Lawton Distinguished Scholar in Chemistry, is the Associate Director of the Clean Energy Institute.  Daniel Gamelin, Harry and Catherine Jaynne Boand Endowed Professor of Chemistry, serves on the Faculty Advisory Board.

New research published in Nature explores organic solar cells

A vial holds a solution that contains the UW-developed polymer “ink” that can be printed to make solar cells.

A vial holds a solution that contains the UW-developed polymer “ink” that can be printed to make solar cells.

David Ginger, Professor and Raymon E. and Rosellen M. Lawton Distinguished Scholar in Chemistry, and Alex Jen, Boeing/Johnson Chair Professor of Materials Science & Engineering, along with other researchers, have recently reported on the role of electron spin in creating efficient organic solar cells. Their findings were recently published in the journal Nature.

Organic solar cells that convert light to electricity using carbon-based molecules have shown promise as a versatile energy source but have not been able to match the efficiency of their silicon-based counterparts. These researchers have discovered a synthetic, high-performance polymer that behaves differently from other tested materials and could make inexpensive, highly efficient organic solar panels a reality. The polymer, created at the University of Washington and tested at the University of Cambridge in England, appears to improve efficiency by wringing electrical current from pathways that, in other materials, cause a loss of electrical charge.

More information can be found at Nature and in the UW News press release.

To learn more about Professor Ginger and Professor Jen, please visit their research group websites.

Ginger Research Group: http://depts.washington.edu/gingerlb/

Jen Research Group: http://depts.washington.edu/jengroup/

Exploring the origins of life

Keller cover image_squareSarah Keller, working with Roy Black, affiliate professor of bioengineering, has helped to unravel some of the mystery surrounding the origin of cells in Earth’s ancient oceans. The work, recently published in the Proceedings of the National Academy of Sciences, describes the unexpected interaction of the chemical components of RNA and fatty acids and their role in stabilizing the precursors to cellular membranes.

The chemical components crucial to the start of life on Earth may have primed and protected each other in never-before-realized ways. That could mean a simpler scenario for how that first spark of life on the planet came about. Scientists have long thought that life started when the right combination of bases and sugars produced self-replicating ribonucleic acid, or RNA, inside a rudimentary ‘cell’ composed of fatty acids. Under the right conditions, fatty acids naturally form into bag-like structures similar to today’s cell membranes. In testing one of the fatty acids representative of those found before life began – decanoic acid – Keller and Black discovered that the four bases in RNA bound more readily to the decanoic acid than did the other seven bases tested. By concentrating more of the bases and sugar that are the building blocks of RNA, the system would have been primed for the next steps, reactions that led to RNA inside a bag.

Descriptions of the published research can be found on the UW News website and on Babbage, the science and technology blog of The Economist.

To learn more about Professor Keller, visit her faculty page and research group website.

The absolute configurations of the bitter acids of hops determined

Werner Kaminsky, Research Associate Professor and Department Crystallographer, working with researchers at KinDex Therapeutics and the University of Washington, has recently determined the absolute configurations of the acids from hops that give beer its characteristic bitter flavor. The results, reported recently in the journal Angewandte Chemie, were determined by X-ray crystallography  of these humulones and isohumulones, as well as several of their derivatives.

Humulones are bacteriostatic bitter substances from hops (Humulus lupulus) and act as natural preservatives. When beer wort is heated together with hops, rearrangement products are formed. These bitter compounds, known as iso-alpha acids or isohumulones, give beer its characteristic flavor. In addition, extracts of hops, such as the more stable tetrahydro-iso-alpha acids used by some brewers instead of hops, have been developed.

When humulones rearrange, a ring containing six carbon atoms converts into a five-membered ring. At the end of this process, two side groups may be arranged in two different ways: They can be on the same side or on opposite sides of the plane of the ring (cis or trans). The determination of the configuration of these compounds was complex because the isomerization process of humulones results in a large number of very similar compounds that had to be separated, purified, and the acids converted into suitable salts.

The absolute configurations of the hops bitter acids found by Kaminsky and his co-workers contradict some of the results previously reported in the literature, which raises the question of how suitable the indirect methods (Horeau method, Cotton effect) used for these studies really are for such investigations. Thanks to their new insights, the researchers have now also been able to determine the mechanism of the rearrangement in detail.

Why is the configuration so interesting? Although excessive beer consumption is not recommended, there are some indications that the hops bitter acids may have positive effects on diabetes, some forms of cancer, and inflammation, as well as weight loss. However, the effects seem to vary substantially depending on the absolute configuration. In addition, the various degrees of bitterness in beer seem to depend on the different forms of the tetrahydro-iso-alpha acids. Now that their stereochemistry is definitively known, these conjectures can be seriously tested, since the binding of iso-alpha acids to proteins requires that their “handedness” be compatible—like nuts and bolts.

To learn more, visit Dr. Kaminsky’s faculty page or read more at Angewandte Chemie.

CENTC receives NSF reauthorization for $20 million

The National Science Foundation has awarded a $20 million grant over five years in reauthorizing the Center for Enabling New Technologies Through Catalysis based at the University of Washington, Department of Chemistry. The center, led by Karen Goldberg, Nicole A. Boand Endowed Professor of Chemistry, brings together 18 investigators and their research groups in chemistry and chemical engineering at 14 different institutions across North America. Their focus is to develop fundamental science needed to sustainably produce chemicals and fuels. Two other UW chemistry professors, James Mayer and Michael Heinekey, are also involved.

The center was established with a three-year NSF grant in 2004 with the aim of finding easier, more powerful and more environmentally friendly ways of manipulating the strong chemical bonds found in most materials. In 2007 the center received a $15 million, five-year award from NSF. Under the latest grant renewal, scientists will create and investigate new reactions and catalyst systems transforming various chemical bonds involving carbon, oxygen and hydrogen. The data will help devise new methods for the chemical industry that could provide consumers with a variety of less-expensive products created in ways that use less energy and produce fewer undesirable byproducts. The research focuses on basic science that can provide the technological basis for sustainable production of chemicals, pharmaceuticals and fuels. The work has significant potential to increase U.S. competitiveness and bring increased energy independence, Goldberg said.

The center offers collaborative training for students as well as postdoctoral researchers. It has a number of industrial affiliates that provide guidance and facilitate commercial development of the center’s research. The Center for Enabling New Technologies Through Catalysis is led by the UW and is funded as part of the NSF Centers for Chemical Innovation program.

Article by of Vince Stricherz, UW News and Information