个人简介

Biophysical Society Thomas E. Thompson Award, 2014 Fellow of the AAAS 2013 UW Postdoctoral Association Mentor Award, 2012 Phi Beta Kappa Visiting Scholar, 2012-2013 Fellow of the American Physical Society, 2011 Elected to Washington State Academy of Sciences, 2011 ASBMB Avanti Young Investigator Award in Lipid Research The Biophysical Society's Margaret Oakley Dayhoff Award UW Department of Chemistry Outstanding Teaching Award Cottrell Teacher-Scholar Award NSF CAREER Award Research Innovation Award (Research Corporation) National Institutes of Health Postdoctoral Fellowship (NRSA) University of California President's Postdoctoral Fellowship

研究领域

Biophysics and Physical Chemistry

Our group investigates a broad array of problems involving self-assembly, complex fluids, and soft matter systems, with an emphasis on lipid membrane biophysics. Below are vignettes of only three of our research topics, followed by general descriptions of our group and techniques. To learn about other projects in our lab, click on the link above for “Keller group website” to access a full list of publications. RESEARCH VIGNETTE 1: Origins of Life (PNAS 2013) A predominant hypothesis regarding how life arose on the young Earth is that the earliest primordial cells consisted of simple fatty acid vesicles encapsulating RNA. In this project, we addressed three fundamental questions: 1) How were nucleobases sufficiently concentrated in early oceans to form RNA? 2) How were the four bases in RNA selected from a heterogeneous environment? 3) How were fatty acid vesicles stabilized against flocculation (aggregation into large clumps) in the salty environments of Earth’s early oceans? Addressing the first two questions, we found that micelles of decanoic acid, a prebiotic fatty acid, bind nucleobases better than most related bases. Addressing the third question, we found that the same bases that bind to decanoic acid micelles stabilize vesicles by inhibiting flocculation. Moreover, the sugar in RNA, ribose, inhibited flocculation better than its stereoisomer, xylose. Our results are exciting because mutually reinforcing mechanisms of bases and sugars binding to fatty acid aggregates, followed by stabilization of vesicles, could have driven the emergence of protocells. RESEARCH VIGNETTE 2: Coarsening of membrane domains (BJ 2013) Here we showed that a simple theory describes the growth rate of domains in membranes far from a critical point, resolving an experimental quandary. We found excellent agreement between our measured growth exponent (0.28 ± 0.05) and the predicted exponent of 1/3. Next, we tested new theories and simulations from 2010 and 2011 regarding how domain sizes evolve in membranes near a miscibility critical point. The simulations predicted that if any well-defined growth exponent could be found in this particular membrane system, then the exponent would have a value of 1/2. We found the exponent to be 0.50 ± 0.16. RESEARCH VIGNETTE 3: Dynamic critical exponents (PRL 2012) Here we repurposed lipid membranes to quantitatively measure a universal physical constant governing time scales of critical correlations. This constant had eluded experimental assessment for over 30 years, despite careful attempts. Our measurement is important because time-dependent critical phenomena are well studied except in systems that have the same constraints as lipid bilayers. Specifically, the constant had been measured in 3-dimensional (3D) systems and in 2D magnets, but never successfully in the broad class of 2D systems that do not behave as magnets. In physics terms, we were the first to accomplish the longstanding goal of measuring the correct dynamic critical exponent of a 2D Ising system with conserved order parameter. We found excellent agreement with the predicted value of the exponent. This prediction was only recently refined in theoretical work in 2008-9. Our measurement is important to biology because other groups have found that membranes derived from intact cell membranes exhibit critical fluctuations. Understanding critical dynamics of membranes is valuable because time scales of composition fluctuations constrain which biological processes may be affected by a membrane’s proximity to a critical point. TECHNIQUES: To tackle the interdisciplinary subjects above, group members come from a range of backgrounds (e.g. physical chemistry, physics, biophysics, and bioengineering) and they earn degrees in a variety of fields. Work in the lab is problem-driven rather than technique-driven, so group members acquire whatever skills are necessary. We collaborate closely with biochemists, and we meet weekly with theory and simulation experts to ensure that our experimental results have strong theoretical foundations (at this time, the group supports no members who conduct solely theory or simulation work). Our group benefits from close proximity to the UW NanoTech User Facility, the UW NNIN Nanofabrication Facility, the UW NESAC/BIO User Facility, and UW Chemistry spectroscopy facilities (mass spec, NMR, and UV/Vis) and machine shops. OUR GROUP: Graduate students and postdocs in the Keller group have written successful NSF, NIH, NASA, and Bettencourt fellowship proposals. They have won national and international awards including the Anna Louise Hoffman Award, the Skinner Prize, Biophysical Society SRAA Awards, Lindau Fellowships, and multiple travel grants. UW has recognized Ph.D. theses in the Keller Group with the Arts & Sciences Dean’s Medal, the Graduate School’s Distinguished Dissertation Award, and the Karrer Prize in Physics.

近期论文

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R.A. Black, D.W. Deamer, M.C. Blosser, B.L. Stottrup, R. Tavakley, and S.L. Keller, Nucleobases bind to and stabilize aggregates of a prebiotic amphiphile, providing a viable mechanism for the emergence of protocells, Proc. Natl. Acad. Sci., 110, 13272-13276, 2013. C.A. Stanich, A.R. Honerkamp-Smith, G.G. Putzel, C.A. Warth, A.K. Lamprecht, P. Mandal, E. Mann, T.D. Hua, and S.L. Keller, Coarsening Dynamics of Domains in Lipid Membranes, Biophys. J., 105, 444-454, 2013. (Cover Article) M.C. Blosser, J.B. Starr, C.W. Turtle, J. Ashcraft, and S.L. Keller, Minimal Effect of Lipid Charge on Membrane Miscibility Phase Behavior in Three Ternary Systems, Biophys. J., 104, 2629-2638, 2013. T. Portet, S.E. Gordon, and S.L. Keller, Increasing Membrane Tension Decreases Miscibility Temperatures, an Experimental Demonstration via Micropipette Aspiration, Biophys. J., 103, L35-37, 2012. (Featured article; free download) A.R. Honerkamp-Smith and S.L. Keller, Experimental Observations of Dynamic Critical Phenomena in a Lipid Membrane, Phys. Rev. Lett, 2012, 108, 165702, 2012. M.M. Stevens, A.R. Honerkamp-Smith and S.L. Keller, Solubility Limits of Cholesterol, Lanosterol, Ergosterol, Stigmasterol and β-Sitosterol in Electroformed Lipid Vesicles, Soft Matter, 6, 5882-5890, 2010. (Cover article) PMCID: PMC3156111 A.R. Honerkamp-Smith, S.L. Veatch, and S.L. Keller, An Introduction to Critical Points for Biophysicists: Observations of Compositional Heterogeneity in Lipid Membranes, Biochim. Biophys. Acta – Biomembr., 1788, 53-63, 2009. (cover article) A.R. Honerkamp-Smith, P. Cicuta, M.D. Collins, S.L. Veatch, M. den Nijs, M. Schick, and S.L. Keller, Line Tensions, Correlation Lengths, and Critical Exponents in Lipid Membranes near Critical Points, Biophys. J., 95, 236-246, 2008. M.D. Collins and S.L. Keller, Tuning Lipid Mixtures to Induce Domains across Leaflets of Unsupported Asymmetric Bilayers, Proc. Natl. Acad. Sci., 105, 124-128, 2008.