Faculty in the Physical Sciences Division at UW Bothell are helping to expand our knowledge of the world through their cutting-edge research. Many faculty use the results of their research to engage stakeholders, such as industry (through drug discovery, for example) and government agencies (for example, on environmental policy).
Faculty Research Projects
Peter Anderson, Computational Modeling in Biochemistry Read more
Dan Jaffe, Atmospheric Chemistry Read more
Joey Shapiro Key, Gravitational Wave Astronomy Read more
Hyung Kim, Chemistry and Biology of Metalloproteins Read more
Lori Robins, Biochemistry Read more
Eric Salathé, Regional Climate Change Read more
Computational Modeling in Biochemistry
Computational modeling of protein structures and their non-covalent interactions with small molecules
The Anderson Group's research currently focuses on two main areas: discovering small molecule inhibitors of lethal pathogens and predicting the effects of human disease-causing mutations.
Combatting Neglected Tropical Diseases
Computational molecular screening is underway to discover small molecule inhibitors of lethal pathogens such as Mycobacterium tuberculosis, the causative agent of tuberculosis. Whereas most traditional drug discovery projects seek to find a single small molecule drug that inhibits a single enzyme, this project seeks to find a single drug that inhibits multiple enzymes from multiple metabolic pathways in the pathogen. This use of polypharmacology has the potential advantage of overcoming or delaying the onset of bacterial drug resistance.
Predicting the Effects of Human Disease-Causing Mutations
The second focus of the Anderson Group is using molecular simulations to predict the effects of human disease-causing mutations on protein structure and function. Single-nucleotide polymorphisms (SNPs), which often cause amino acid mutations in human proteins, play a role in the development of many diseases, including cancer, Parkinson’s disease, and neurological and endocrine disorders. Modeling these amino acid mutations with high-level molecular dynamics simulations can predict their effects on protein structure and dynamics, providing clues about the molecular mechanisms underlying disease onset.
Back to top
Local, regional, and global sources of pollution in the Western US, with an emphasis on ozone, aerosols, and mercury
The Jaffe Group mission is to study and understand the sources of pollution and to understand the chemical processing of these pollutants and their links to climate change. These issues are important because air quality is a central ingredient to quality of life. Bad air contributes to many health problems and premature mortality. Since 2004, we have maintained a research station at the top of Mt. Bachelor in central Oregon. Specific areas of research are:
Local and regional sources of pollution
Global transport of pollutants from Asia to the US.
Natural sources of pollutants, such as wildfires or stratospheric intrusions
Sources of Hg0(g) to the atmosphere and the environment
Sources of CO2, diesel soot, nitrogen oxides, and coal dust from trains in Washington State
Students are involved at all levels of the research including calibrating instrumentation, doing fieldwork, analyzing the data, and working on scientific papers. Many undergraduates have been coauthors on our papers and presented at regional and national conferences and meetings.
Jaffe Group website
Back to top
Joey Shapiro Key
Gravitational Wave Astronomy
Detecting gravitational waves and characterizing the sources
The UWB Gravitational Wave Astronomy group works on projects related to gravitational wave astronomy data analysis and parameter estimation. We are members of international collaborations to observe gravitational waves and characterize the sources. The Laser Interferometer Gravitational wave Observatory (LIGO) is a ground-based gravitational wave detector that made the first direct observation of a gravitational wave signal from a binary black hole collision on September 14, 2015. The UWB Gravitational Wave Astronomy group is a member of the LIGO Scientific Collaboration (LSC) working on data analysis, detector characterization, parameter estimation, and LSC education and public outreach efforts. The group is also a member of the North American Nanohertz Observatory for Gravitational waves (NANOGrav) collaboration to detect gravitational waves using a pulsar timing array (PTA). We also work on projects for the future joint European Space Agency (ESA) and NASA Laser Interferometer Space Antenna (LISA) mission to detect gravitational waves from space.
Back to top
Chemistry and Biology of Metalloproteins
Spectroelectrochemistry of metalloproteins, assembly dynamics of supramolecular metalloprotein complexes, and intracellular heme trafficking
Nature utilizes the chemical properties of transition metal ions for a variety of cellular processes that drive life. The association of these metal ions with proteins allows key reactions to occur that are otherwise unachievable with proteins alone. These include electron transfer, O2 and other small molecule transport, and catalytic transformations of very stable molecules such as methane to methanol.
Research in the Kim laboratory has a special interest in these metalloproteins that contain copper and iron (as heme). We use an interdisciplinary approach, including chemical and biological tools, to study their functions and properties. For example, spectroelectrochemistry is used to determine the redox potentials of multi-heme centers in electron-transfer proteins. We also determine the identities of intermediate species in redox reactions. We employ biochemical tools to analyze protein-protein interactions between metalloproteins to deduce long-range electron transfer pathways. We purify the proteins needed for our studies from ammonia- and methane-oxidizing bacteria that are of environmental significance.
Our laboratory is also interested in elucidating the intracellular trafficking mechanism of metal-containing cofactors, in particular heme. The chemical properties of heme that are so useful in biology also create toxicity issues when the heme is “free” inside the cell. Thus, we are interested in uncovering the cellular pathways that enable heme, and its biosynthetic intermediates, to be safely trafficked to their target locations. We use yeast as a model system for this aspect of our research.
Back to top
Using kinetic isotope effects and protein modifications to understand biological reactions such as DNA cleavage and thioester hydrolysis
The Robins lab focuses on understanding biological mechanisms. Current research projects focus on three areas:
Determining the Mechanism of Thioester Hydrolysis
Thioesters are important to synthetic organic chemists due to their enhanced reactivity. In biochemistry, thioesters are used for a variety of metabolic reactions including acyl-transfer and hydrolysis reactions. One of the most common thioesters is acetyl-CoA. Interestingly, the mechanism of thioester hydrolysis is unclear. We aim to elucidate the mechanism of thioester hydrolysis. We use kinetic isotope effects to compare thioester hydrolysis of enzyme-catalyzed and non-catalyzed reactions.
Identification of Inhibitors of Helicobacter pylori Aldo-Keto Reductase
Helicobacter pylori can survive in the extremely acidic conditions of the gastric mucous, which can lead to peptic ulcer formation and various types of cancer. The treatments for H. pylori infection are decreasing in effectiveness due to the identification of antibiotic resistant strains of H. pylori. We are working to identify possible inhibitors for H. pylori aldo-keto reductase (HpAKR), an enzyme required for H. pylori survival in acidic conditions. Identified inhibitors are tested for activity against HpAKR.
Determining the Mechanism of Enzyme-Catalyzed DNA Hydrolysis by Homing Endonucleases
Genetic modification can be used as a tool to selectively correct the sequence of a dysfunctional gene responsible for a genetic disease, such as sickle cell anemia or hemophilia. As a biotechnology tool, targeted genetic modification can be employed to create engineered microbes or plants that can be used for bioremediation, biofuel production, or the creation of crop species with improved traits. One family of enzymes used for genetic modification is homing endonucleases. We are working to understand how homing endonucleases cleave DNA and to develop a method to transform homing endonucleases into nicking endonucleases to generate enzymes that can make single strand breaks in DNA.
Undergraduate research students are involved in all aspects of the Robins research program. Students conduct literature searches and develop experimental procedures. They also learn how to collect and analyze data and present their results.
Back to top
Regional Climate Change
Improving global climate models by focusing on regional climate change in the US Pacific Northwest
The goal of this research is to transform our knowledge of global climate change into information suitable for understanding and preparing for the impacts of climate change.
Scenarios of global climate change and variability are the foundation for our knowledge about the climate. These scenarios are produced by global climate models, which are the same as weather models, but run 100 years into the future. Global models, however, represent the atmosphere and surface much too coarsely to simulate regional processes, such as precipitation and streamflow, that determine the effects of climate on the region. Furthermore, global models do not account for surface features, such as topography and land use, that determine the regional climate.
We have been using a regional climate model and statistical methods to improve on these scenarios. The resulting detailed information is being used by organizations as they plan for the future in a changed climate. Students can become involved at any stage in this process, from building computer models to working with communities!
Eric Salathé's website