Justin Ashworth

Contact

206 732 2179
justin.ashworth@systemsbiology.org

Position
Postdoctoral Fellow
Degree
PhD, Biochemistry, University of Washington, Dec 2009
Areas of Expertise
Computational Biology; systems biology; biochemistry; molecular inference; modeling, prediction, and design of protein structure/function; genome engineering; transcriptomics; gene regulatory inference; systems biology of marine microeukaryotes (diatoms), microbial reverse-engineering including 'non-model' species, in vitro characterization; X-ray crystallography; nucleic acids work
Links

Research Highlights

I am interested in the modeling and prediction of molecular and genetic variations in cellular systems, and the ways in which the functions and interactions of genetically encoded molecules are "designed" in nature to yield cellular physiologies and adaptations. Recently I have been studying gene regulation of new microorganisms and the functional roles of mutations in cellular systems in order to relate our biophysical understanding of molecular function and evolution to systems-level characteristics.

Ocean Acidification and Diatoms

Marine phytoplankton, including diatoms, are prolific producers in the ocean that form the basis of food webs in coastal and ocean upwelling areas and have a major role in global carbon cycles. The goal of this project is to understand the systems biology of diatoms and the impact of ocean acidification and other stressors on their molecular and adaptive physiology. We are generating descriptive and predictive models of gene expression in response to projected environmental scenarios to a changing and acidifying ocean. A combination of bioinformatics, laboratory and field studies are being used gain an unbiased, systems-level understanding of the response of diatoms to ocean acidification.

How Regulatory Genetic Diversity Drives Cellular Physiology

A large portion of cellular physiology and adaptation depends upon the finely tuned molecular interactions that constitute gene regulatory networks. Genetic variability of the components that participate in these interactions is highly apparent, and is likely responsible for a significant portion of the differences in biology between closely related organisms. A complete understanding of (and ability to predict) the consequences of genetically encoded regulatory variation requires a molecular model of functional change, and a means of extrapolating its effect to changes in systems-level cellular behavior. This can be accomplished by analyzing the molecular variability of regulatory elements within the context of known large-scale regulatory networks.

Publications

Other Publications

Stittrich AB, Lehman A, Bodian DL, Ashworth J, Zong Z, Li H, Lam P, Khromykh A, Iyer RK, Vockley JG, Baveja R, Silva ES, Dixon J, Leon EL, Solomon BD, Glusman G, Niederhuber JE*, Roach JC, Patel MS*. (2014) Mutations in NOTCH1 cause Adams-Oliver Syndrome. Am J Hum Genet. 95(3):275-84.
Thyme SB*, Boissel SJS, Quadri SA, Nolan T, Baker DA, Park RU, Kusak L, Ashworth J, Baker D*. (2014) Reprogramming homing endonuclease specificity through computational design and directed evolution. Nucleic Acids Res. 42(4):2564-2576.
Fleishman SJ*, Leaver-Fay AP, Corn JE, Strauch EM, Khare SD, Koga N, Ashworth J, Murphy P, Richter F, Lemmon G, Baker D*. (2011) RosettaScripts: an XML-like interface to the Rosetta macromolecular modeling suite. PloS One 6(6):e20161.
Thyme SB*, Jarjour J, Takeuchi R, Havranek JJ, Ashworth J, Scharenberg AM, Stoddard BL, Baker D*. (2009) Exploitation of binding energy for catalysis and design. Nature 461, 1300 –1304. PMID: 19865174, PMC2771326.
Ashworth J* and Baker D*. (2009) Assessment of the optimization of affinity and specificity at protein-DNA interfaces. Nucleic Acids Res. 37(10), e73. PMID: 19389725, PMC2691843.
Eastberg, J.H., Smith, A.M., Zhao, L., Ashworth, J., Shen, B.W., Stoddard, B.L*. (2007) Thermodynamics of DNA target site recognition by homing endonucleases. Nucleic Acids Res. 35, 7209 –21. PMID: 17947319, PMC2175346.
Bateman RL, Ashworth J, Witte JF, Baker LJ, Bhanumoorthy P, Timm DE, Hurley TD, Grompe M, McClard RW*. (2007) Slow-onset inhibition of fumarylacetoacetate hydrolase by phosphinate mimics of the tetrahedral intermediate: kinetics, crystal structure and pharmacokinetics. Biochem J 402(2): 251-60.
Ashworth J*, Havranek JJ, Duarte CM, Sussman D, Monnat RJ, Stoddard BL, Baker D*. (2006) Computational redesign of endonuclease DNA binding and cleavage specificity. Nature 441(7093), 656 –9. PMID: 16738662, PMC2999987.