Sarah L. Keller

Last updated
Sarah L. Keller
NationalityAmerican
Alma mater Rice University, Princeton University
AwardsThomas E. Thompson Award (2014); Avanti Award in Lipids (Biophysical Society, 2017)
Scientific career
FieldsBiophysics
Institutions University of Washington
Doctoral advisor Sol M. Gruner

Sarah L. Keller is an American biophysicist, studying problems at the intersection between biology and chemistry. She investigates self-assembling soft matter systems. [1] [2] [3] Her current main research focus is understanding how simple lipid mixtures within bilayer membranes give rise to membrane's complex phase behavior. [4] [5] [6] [7]

Contents

Keller is a fellow of the American Physical Society (APS) (2011) [8] and the American Association for the Advancement of Science (AAAS) (2013) and has won multiple awards including the Thomas E. Thompson Award (2014) [9] and the Avanti Award in Lipids (Biophysical Society, 2017). [10] She is a professor of chemistry and adjunct professor of physics at the University of Washington, Seattle, WA. [11]

Early life and education

Keller studied her undergraduate degree at Rice University and gained her Ph.D degree in Physics at Princeton University in 1995. Her graduate study was on the "interaction between Ion-channels and Lipid Membranes", supervised by Dr. Sol M. Gruner. She was a postdoctoral researcher at University of California Santa Barbara and Stanford University before becoming professor at University of Washington. [11]

Major publications

Keller studies the organization of lipids in membranes. [11] [12] [13] Cell membranes are composed of lipids and proteins. Her early work "Separation of liquid phases in giant vesicles of ternary mixtures of phospholipids and cholesterol" [4] used fluorescence microscopy to observe a mixture of saturated and unsaturated lipids and observed microscopic separations of two coexisting liquid phases—miscibility transition. Her works contributed to models of protein aggregation within membranes and the theory of membrane lateral pressure. [14]

Her recent work "Hallmarks of Reversible Separation of Living, Unperturbed Cell Membranes into Two Liquid Phases" found reversible phase separations over multiple warming and cooling cycles in yeast vacuoles, taking a step further towards conditions in living cells. [15]

Because early life has the simple form of RNA encapsulated by fatty acid, Keller's work could also explore mysteries about the origin of life. [16]

Awards and honors

Keller was awarded the University of Washington Distinguished Teaching Award in 2006 [23] and the department of chemistry Outstanding Teaching Award in 2004.

Related Research Articles

Cytoplasm All of the contents of a eukaryotic cell except the nucleus

In cell biology, the cytoplasm is all of the material within a cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The main components of the cytoplasm are cytosol, the organelles, and various cytoplasmic inclusions. The cytoplasm is about 80% water and usually colorless.

Detergent surfactants with cleansing properties, even in dilute solutions

A detergent is a surfactant or a mixture of surfactants with cleansing properties in dilute solutions. These substances are usually alkylbenzene sulfonates, a family of compounds that are similar to soap but are more soluble in hard water, because the polar sulfonate is less likely than the polar carboxylate to bind to calcium and other ions found in hard water.

Lipid bilayer A thin polar membrane made of two layers of lipid molecules

The lipid bilayer is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many viruses are made of a lipid bilayer, as are the nuclear membrane surrounding the cell nucleus, and membranes of the membrane-bound organelles in the cell. The lipid bilayer is the barrier that keeps ions, proteins and other molecules where they are needed and prevents them from diffusing into areas where they should not be. Lipid bilayers are ideally suited to this role, even though they are only a few nanometers in width, because they are impermeable to most water-soluble (hydrophilic) molecules. Bilayers are particularly impermeable to ions, which allows cells to regulate salt concentrations and pH by transporting ions across their membranes using proteins called ion pumps.

Lipid raft

The plasma membranes of cells contain combinations of glycosphingolipids, cholesterol and protein receptors organised in glycolipoprotein lipid microdomains termed lipid rafts. Their existence in cellular membranes remains somewhat controversial. It has been proposed that they are specialized membrane microdomains which compartmentalize cellular processes by serving as organising centers for the assembly of signaling molecules, allowing a closer interaction of protein receptors and their effectors to promote kinetically favorable interactions necessary for the signal transduction. Lipid rafts influence membrane fluidity and membrane protein trafficking, thereby regulating neurotransmission and receptor trafficking. Lipid rafts are more ordered and tightly packed than the surrounding bilayer, but float freely within the membrane bilayer. Although more common in the cell membrane, lipid rafts have also been reported in other parts of the cell, such as the Golgi apparatus and lysosomes.

Gramicidin

Gramicidin, also called gramicidin D, is a mix of ionophoric antibiotics, gramicidin A, B and C, which make up about 80%, 5%, and 15% of the mix, respectively. Each has 2 isoforms, so the mix has 6 different types of gramicidin molecules. They can be extracted from Brevibacillus brevis soil bacteria. Gramicidins are linear peptides with 15 amino acids. This is in contrast to unrelated gramicidin S, which is a cyclic peptide.

Calcium-induced calcium release (CICR) describes a biological process whereby calcium is able to activate calcium release from intracellular Ca2+ stores (e.g., endoplasmic reticulum or sarcoplasmic reticulum). Although CICR was first proposed for skeletal muscle in the 1970s, it is now known that CICR is unlikely to be the primary mechanism for activating SR calcium release. Instead, CICR is thought to be crucial for excitation-contraction coupling in cardiac muscle. It is now obvious that CICR is a widely occurring cellular signaling process present even in many non-muscle cells, such as in the insulin-secreting pancreatic beta cells, epithelium, and many other cells. Since CICR is a positive-feedback system, it has been of great interest to elucidate the mechanism(s) responsible for its termination.

Erich Sackmann

Erich Sackmann is a German experimental physicist and a pioneer of biophysics in Europe.

Membrane fusion is a key biophysical process that is essential for the functioning of life itself. It is defined as the event where two lipid bilayers approach each other and then merge to form a single continuous structure. In living beings, cells are made of an outer coat made of lipid bilayers; which then cause fusion to take place in events such as fertilization, embryogenesis and even infections by various types of bacteria and viruses. It is therefore an extremely important event to study. From an evolutionary angle, fusion is an extremely controlled phenomenon. Random fusion can result in severe problems to the normal functioning of the human body. Fusion of biological membranes is mediated by proteins. Regardless of the complexity of the system, fusion essentially occurs due to the interplay of various interfacial forces, namely hydration repulsion, hydrophobic attraction and van der Waals forces.

One property of a lipid bilayer is the relative mobility (fluidity) of the individual lipid molecules and how this mobility changes with temperature. This response is known as the phase behavior of the bilayer. Broadly, at a given temperature a lipid bilayer can exist in either a liquid or a solid phase. The solid phase is commonly referred to as a “gel” phase. All lipids have a characteristic temperature at which they undergo a transition (melt) from the gel to liquid phase. In both phases the lipid molecules are constrained to the two dimensional plane of the membrane, but in liquid phase bilayers the molecules diffuse freely within this plane. Thus, in a liquid bilayer a given lipid will rapidly exchange locations with its neighbor millions of times a second and will, through the process of a random walk, migrate over long distances.

Lipid bilayer fusion

In membrane biology, fusion is the process by which two initially distinct lipid bilayers merge their hydrophobic cores, resulting in one interconnected structure. If this fusion proceeds completely through both leaflets of both bilayers, an aqueous bridge is formed and the internal contents of the two structures can mix. Alternatively, if only one leaflet from each bilayer is involved in the fusion process, the bilayers are said to be hemifused. In hemifusion, the lipid constituents of the outer leaflet of the two bilayers can mix, but the inner leaflets remain distinct. The aqueous contents enclosed by each bilayer also remain separated.

A model lipid bilayer is any bilayer assembled in vitro, as opposed to the bilayer of natural cell membranes or covering various sub-cellular structures like the nucleus. They are used to study the fundamental properties of biological membranes in a simplified and well-controlled environment, and increasingly in bottom-up synthetic biology for the construction of artificial cells. A model bilayer can be made with either synthetic or natural lipids. The simplest model systems contain only a single pure synthetic lipid. More physiologically relevant model bilayers can be made with mixtures of several synthetic or natural lipids.

WALP peptide Class of peptides used for studying lipid membranes

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Saffman–Delbrück model Mathematical model of lipid membranes

The Saffman–Delbrück model describes a lipid membrane as a thin layer of viscous fluid, surrounded by a less viscous bulk liquid. This picture was originally proposed to determine the diffusion coefficient of membrane proteins, but has also been used to describe the dynamics of fluid domains within lipid membranes. The Saffman–Delbrück formula is often applied to determine the size of an object embedded in a membrane from its observed diffusion coefficient, and is characterized by the weak logarithmic dependence of diffusion constant on object radius.

John A. Quinn

John A. Quinn, Ph.D. was the Robert D. Bent Professor Emeritus of Chemical and Biomolecular Engineering at the University of Pennsylvania School of Engineering and Applied Science. He was a leader in the fields of mass transfer and membrane transport in synthetic membranes since the 1960s. In the early phase of his career at the University of Illinois, Quinn and his students devised simple, elegant experiments to elucidate the role of the interface in mass transfer between phases. In later work at Penn, he applied these insights to problems of engineering and biological significance involving chemical reaction and diffusion within and through both finely porous and reactive membranes. His chemical engineering science has informed matters as far afield as the separation of chiral pharmaceuticals and the behavior of cells at interfaces.

Laurdan Chemical compound

Laurdan is an organic compound which is used as a fluorescent dye when applied to fluorescence microscopy. It is used to investigate membrane qualities of the phospholipid bilayers of cell membranes. One of its most important characteristics is its sensitivity to membrane phase transitions as well as other alterations to membrane fluidity such as the penetration of water.

A unilamellar liposome is a spherical chamber/vesicle, bounded by a single bilayer of an amphiphilic lipid or a mixture of such lipids, containing aqueous solution inside the chamber. Unilamellar liposomes are used to study biological systems and to mimic cell membranes, and are classified into three groups based on their size: small unilamellar liposomes/vesicles (SUVs) that with a size range of 20–100 nm, large unilamellar liposomes/vesicles (LUVs) with a size range of 100–1000 nm and giant unilamellar liposomes/vesicles (GUVs) with a size range of 1-200 µm. GUVs are mostly used as models for biological membranes in research work. Animal cells are 10–30 µm and plant cells are typically 10–100 µm. Even smaller cell organelles such as mitochondria are typically 1-2 µm. Therefore, a proper model should account for the size of the specimen being studied. In addition, the size of vesicles dictates their membrane curvature which is an important factor in studying fusion proteins. SUVs have a higher membrane curvature and vesicles with high membrane curvature can promote membrane fusion faster than vesicles with lower membrane curvature such as GUVs.

Geraldine L. Richmond American chemist and physicist

Geraldine Lee Richmond is an American chemist and physical chemist who is President Joe Biden's nominee to serve as Under Secretary of Energy for Science in the US Department of Energy. Richmond is the Presidential Chair in Science and Professor of Chemistry at the University of Oregon (UO). She conducts fundamental research to understand the chemistry and physics of complex surfaces and interfaces. These understandings are most relevant to energy production, atmospheric chemistry and remediation of the environment. Throughout her career she has worked to increase the number and success of women scientists in the U.S. and in many developing countries in Africa, Asia and South America. Richmond has served as president of the American Association for the Advancement of Science, and she received the 2013 National Medal of Science.

Biomolecular condensate

Biomolecular condensates are a class of non-membrane bound organelles and organelle subdomains, specified by physical concepts that date back a long way. As with other organelles, biomolecular condensates are specialized subunits of the cell. However, unlike many organelles, biomolecular condensate composition is not controlled by a bounding membrane. Instead they can form through a range of different processes, the most well-known of which is phase separation of proteins, RNA and other biopolymers into either colloidal emulsions, liquid crystals, solid crystals or aggregates within cells.

Ka Yee Christina Lee is a Professor of Chemistry and the Provost at the University of Chicago, where she succeeded Daniel Diermeier on February 1, 2020. She works on membrane biophysics, including protein–lipid interactions, Alzheimer's disease and respiratory distress syndrome. She is a Fellow of the American Institute for Medical and Biological Engineering and American Physical Society.

Sarah Louise Veatch is an American biophysicist, associate professor of biophysics at University of Michigan.

References

  1. ↑ Keller, Sarah L.; McConnell, Harden M. (1999-02-15). "Stripe Phases in Lipid Monolayers near a Miscibility Critical Point". Physical Review Letters. 82 (7): 1602–1605. Bibcode:1999PhRvL..82.1602K. doi:10.1103/PhysRevLett.82.1602. ISSN   0031-9007.
  2. ↑ Adams, Marie; Dogic, Zvonimir; Keller, Sarah L.; Fraden, Seth (May 1998). "Entropically driven microphase transitions in mixtures of colloidal rods and spheres". Nature. 393 (6683): 349–352. Bibcode:1998Natur.393..349A. doi:10.1038/30700. ISSN   0028-0836. S2CID   1676273.
  3. ↑ "Keller Research Group: University of Washington". faculty.washington.edu. Retrieved 2019-03-08.
  4. 1 2 Keller, Sarah L.; Veatch, Sarah L. (2003-11-01). "Separation of Liquid Phases in Giant Vesicles of Ternary Mixtures of Phospholipids and Cholesterol". Biophysical Journal. 85 (5): 3074–3083. Bibcode:2003BpJ....85.3074V. doi:10.1016/S0006-3495(03)74726-2. ISSN   0006-3495. PMC   1303584 . PMID   14581208.
  5. ↑ Veatch, Sarah L.; Keller, Sarah L. (2002-12-09). "Organization in Lipid Membranes Containing Cholesterol". Physical Review Letters. 89 (26): 268101. Bibcode:2002PhRvL..89z8101V. doi:10.1103/PhysRevLett.89.268101. ISSN   0031-9007. PMID   12484857.
  6. ↑ Stanich, Cynthia A.; Honerkamp-Smith, Aurelia R.; Putzel, Gregory Garbès; Warth, Christopher S.; Lamprecht, Andrea K.; Mandal, Pritam; Mann, Elizabeth; Hua, Thien-An D.; Keller, Sarah L. (July 2013). "Coarsening Dynamics of Domains in Lipid Membranes". Biophysical Journal. 105 (2): 444–454. Bibcode:2013BpJ...105..444S. doi:10.1016/j.bpj.2013.06.013. PMC   3714885 . PMID   23870265.
  7. ↑ Cornell, Caitlin E.; Skinkle, Allison D.; He, Shushan; Levental, Ilya; Levental, Kandice R.; Keller, Sarah L. (August 2018). "Tuning Length Scales of Small Domains in Cell-Derived Membranes and Synthetic Model Membranes". Biophysical Journal. 115 (4): 690–701. Bibcode:2018BpJ...115..690C. doi:10.1016/j.bpj.2018.06.027. PMC   6103737 . PMID   30049406.
  8. 1 2 "APS Fellow Archive". www.aps.org. Retrieved 2019-03-04.
  9. 1 2 Goñi, Felix M.; Longo, Marjorie (2014). "Subgroups MSAS". Biophysical Newsletter. p. 12. Retrieved 16 August 2020.CS1 maint: discouraged parameter (link)
  10. ↑ "Avanti Awards in Lipids". Avanti Polar Lipids. Retrieved 2019-03-04.
  11. 1 2 3 "Sarah L. Keller - UW Dept. of Chemistry". depts.washington.edu. Retrieved 2019-03-04.
  12. ↑ Miller, Johanna L. (February 2018). "Membrane phase demixing seen in living cells". Physics Today. 71 (2): 21–23. Bibcode:2018PhT....71b..21M. doi:10.1063/PT.3.3838. ISSN   0031-9228.
  13. ↑ "Demixing in cell membranes". Physics Today. 2017. doi:10.1063/PT.6.1.20171221a.
  14. ↑ "Keller Garners Avanti Young Investigator Award". www.asbmb.org. Retrieved 2019-03-04.
  15. ↑ Rayermann, Scott P.; Rayermann, Glennis E.; Cornell, Caitlin E.; Merz, Alexey J.; Keller, Sarah L. (December 2017). "Hallmarks of Reversible Separation of Living, Unperturbed Cell Membranes into Two Liquid Phases". Biophysical Journal. 113 (11): 2425–2432. Bibcode:2017BpJ...113.2425R. doi:10.1016/j.bpj.2017.09.029. PMC   5768487 . PMID   29211996.
  16. ↑ Yong, Ed (August 12, 2019). "A New Clue to How Life Originated". The Atlantic. Retrieved 16 August 2020.CS1 maint: discouraged parameter (link)
  17. ↑ "Society Names 2021 Fellows". Biophysical Society. Retrieved November 4, 2020.
  18. ↑ "Biophysical Society Names 2017 Award Recipients" (PDF). Biophysical Society. August 2, 2016. Retrieved 16 August 2020.CS1 maint: discouraged parameter (link)
  19. ↑ "AAAS Members Elected as Fellows". American Association for the Advancement of Science. Retrieved 16 August 2020.CS1 maint: discouraged parameter (link)
  20. ↑ American Society for Biochemistry and Molecular Biology (10 December 2009). "University of Washington professor garners Avanti Young Investigator Award". EurekaAlert. American Association for the Advancement of Science (AAAS). Retrieved 16 August 2020.CS1 maint: discouraged parameter (link)
  21. ↑ ASBMB LIPID RESEARCH DIVISION (2010). "Exploring Membranes: The Work of Sarah L. Keller" (PDF). ASBMB Today (June). p. 32. Retrieved 2020-08-16.
  22. ↑ "Avanti Awards in Lipids". Avanti. 2010. Retrieved 16 August 2020.CS1 maint: discouraged parameter (link)
  23. ↑ "Previous award recipients | Center for Teaching and Learning" . Retrieved 2019-03-04.
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