Sarah L. Keller | |
---|---|
Nationality | American |
Alma mater | Rice University, Princeton University |
Awards | Thomas E. Thompson Award (2014); Avanti Award in Lipids (Biophysical Society, 2017) |
Scientific career | |
Fields | Biophysics |
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]
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]
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]
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] one of the most cited papers in the Biophysical Journal, [14] 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. [15]
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. [16] Keller's follow-up work detailed that this transition is regulated by yeast and corresponds to their growth temperatures. [17] [18] [19]
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. [20]
Keller was awarded the University of Washington Distinguished Teaching Award in 2006 [34] and the department of chemistry Outstanding Teaching Award in 2004.
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.
The fluid mosaic model explains various characteristics regarding the structure of functional cell membranes. According to this biological model, there is a lipid bilayer in which protein molecules are embedded. The phospholipid bilayer gives fluidity and elasticity to the membrane. Small amounts of carbohydrates are also found in the cell membrane. The biological model, which was devised by Seymour Jonathan Singer and Garth L. Nicolson in 1972, describes the cell membrane as a two-dimensional liquid where embedded proteins are generally randomly distributed. For example, it is stated that "A prediction of the fluid mosaic model is that the two-dimensional long-range distribution of any integral protein in the plane of the membrane is essentially random."
Lipidomics is the large-scale study of pathways and networks of cellular lipids in biological systems. The word "lipidome" is used to describe the complete lipid profile within a cell, tissue, organism, or ecosystem and is a subset of the "metabolome" which also includes other major classes of biological molecules. Lipidomics is a relatively recent research field that has been driven by rapid advances in technologies such as mass spectrometry (MS), nuclear magnetic resonance (NMR) spectroscopy, fluorescence spectroscopy, dual polarisation interferometry and computational methods, coupled with the recognition of the role of lipids in many metabolic diseases such as obesity, atherosclerosis, stroke, hypertension and diabetes. This rapidly expanding field complements the huge progress made in genomics and proteomics, all of which constitute the family of systems biology.
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 controversial. Indeed, Kervin and Overduin imply that lipid rafts are misconstrued protein islands, which they propose form through a proteolipid code. Nonetheless, 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.
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Single-particle tracking (SPT) is the observation of the motion of individual particles within a medium. The coordinates time series, which can be either in two dimensions (x, y) or in three dimensions (x, y, z), is referred to as a trajectory. The trajectory is typically analyzed using statistical methods to extract information about the underlying dynamics of the particle. These dynamics can reveal information about the type of transport being observed (e.g., thermal or active), the medium where the particle is moving, and interactions with other particles. In the case of random motion, trajectory analysis can be used to measure the diffusion coefficient.
In colloidal chemistry, 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.
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.
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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.
Tobias C. Walther is the chair of the cell biology program at Sloan Kettering Institute in New York City and a professor at Weill Cornell School of Medicine, where he co-directs the Farese and Walther lab. He has been a Howard Hughes Medical Institute investigator since 2015. His primary responsibilities are to provide leadership in research and teaching in the scientific fields of metabolism, membrane biology and lipids.
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In biochemistry, biomolecular condensates are a class of membrane-less organelles and organelle subdomains, which carry out specialized functions within the cell. Unlike many organelles, biomolecular condensate composition is not controlled by a bounding membrane. Instead, condensates can form and maintain organization 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, gels, liquid crystals, solid crystals or aggregates within cells.
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