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Miller institute newsletter Winter 2010 Miller Fellow Focus: Eva Schmid into tissues and organs. For this to fame in the lab. The most reason, cells are often called ‘the widely used are the bacterium building blocks of life’. Cells Escherichia coli, the bakers yeast come in many shapes and sizes. Sacchharomyces cerevisiae, the They range from tiny bacteria fruit flyDrosophila melanogaster, about 1 µm in length, to nerve the worm Caenorhaptidis elegans, cells in giraffes that can grow up the slime mould Dictyostelium to 3 meters long or to the colossal discoideum, the plant Arabidopsis 3 pound single cell comprising an thaliana and the house mouse Mus unfertilized ostrich egg. Similar musculus. Each one of them has diversity becomes apparent when made great discoveries possible by looking at cellular functions. Cells being a simpler model for a more have become masters at adapting complex cellular, developmental, to their surroundings in order neurological or behavioral to survive in the unlikeliest of phenomenon. But even though conditions. those model systems are much simpler than for example the One of the most memorable As diverse as cells are, they have human body, a redwood forest or experiences for a biologist in some fundamental features in a coral reef, they are still living training is the first look through common. Functionally, they all systems, which are not completely a microscope. The object of need to grow and divide. They understood and also not 100% observation could be a human need to communicate with their controllable. There is a need for an hair or a small spider, but no surroundings, sense changes and even more reductionist approach matter what it is, it is fascinating react accordingly. Structurally, in biology. The interdisciplinary and a little scary. One immediately all cells have a ‘skin’ called collaboration of biologists, realizes that there is a whole new the plasma membrane, which chemists, physicist and more world of detail opening up in front separates the cell’s interior from recently, engineers, has led to the of one’s eyes. Glimpses of this the environment. On the inside emergence of a new field known world were first seen in the 1600s are the working parts, which continued on page 2 by Robert Hooke and Antonie enable the cell to metabolize and van Leeuwenhoek, who took a replicate, change shape, move, big step towards the biology that produce defense molecules, INSIDE THIS EDITION is still taught in school today. communicate and interact with Their observations were further their surroundings, as well as Miller Fellow Focus 1 developed by Theodor Schwann perform many, many more general and Matthias Schleiden, leading or cell-specific functions. Miller Senior Fellowship 3 to the ‘cell theory’, which stated: The Advisory Board 4 “All living things or organisms are In order to understand biological Miller Professorships 4 made of cells.” functions, biologists have often turned to so-called ‘model Visiting Professorships 4 We now know that some cells are systems’. Those are cells or Awards and Honors 5 organisms unto themselves (such organisms that are experimentally Publications 5 as bacteria or amoeba), while other tractable in the lab and give organisms evolved to live as a insight into specific biological Announcements 6 carefully orchestrated consortium questions. So it happened that of cells, which further specialized some selected organisms came The Adolph C. and Mary Sprague Miller Institute for Basic Research in Science University of California, Berkeley input (signaling molecule) chassis (unilamellar vesicle) signal transmission output (transmembrane (shape change) receptor) signal processing (protein expression) cell cell-mimic Figure 1: Building cell-like devices. The complexity that underlies cellular fuctions makes cells notoriously dicult to understand and control. The reconstitution of biological processes outside a living system in the form of highly simplied cellular mimics will aid in the understanding of isolated processes. continued from page 1 that enabled the encapsulation of bio-molecules within by the names of reconstitutive biology or synthetic membranous compartments, thereby fulfilling the first biology. This field is summarized well with the often- requirement of a cell-like system. cited Feynman quote: “What I cannot create, I do not understand.” It is taking a novel, complementary How is that achieved? The technical principle is approach to traditional experimental biology. Rather somewhat similar to blowing soap bubbles. Just instead than taking cells apart to understand cellular functions, of air deforming a soap film, a fluid jet (generated scientists now attempt to mimic biological functions by a piezo-controlled inkjet) deforms a planar lipid by building them from basic parts (Figure 1). This bilayer, thereby simultaneously creating and loading approacha has great implications in basic research since unilamellar vesicles (Figure 2). In order to achieve it puts existing models of biological functions to the the second requirement there is the need to engineer test: if we really understand how a process works, a sensor system into the vesicles. This is done by and know all its components, we should be able to incorporating transmembrane proteins into the lipid build it from scratch. Furthermore, if we can indeed membrane, thereby enabling controlled50um communication reconstitute biological functions in the lab, a wide between ‘outside’ and ‘inside’. Although it sounds field of applications in healthcare, energy and material straightforward, this task is technically20x confocal challenging science comes into reach. because membrane proteins are verymicroscopy hard to produce of insertedand work with. Eva and her colleaguesGFP-tagged succeeded Eva Schmid, a second year Miller Fellow in the in demonstrating the proof of principle with simple lipid bilayer TM protein Department of Bioengineering, is using this approach transmembrane proteins initially (FigureTM protein 2a) and are to move closer towards a new model system, a working towards more challengingin systems. vesicle While this ‘synthetic cell-like system’. Such a system aims to is still in progress, the third and fourthmembrane requirement will form the basis for a widely applicable method to test be approached simultaneously. The team works on a biological models. The system will have to encompass system to enable the vesicle to produce proteins (Figure a basicb setup of functions: (1) compartmentalizationGFP expression2b), which should lead to a change in vesicle shape. of biological components within micron-sized lipid Finally, once all individual steps can be reproducibly bilayer vesicle, separating ‘inside’ from ‘outside’; performed they can be combined and generate the first (2) a sensory system, which recognizes a signal from functional cell-like system, translating an external input the outside and transmits it to the inside; (3) a signal into a visually detectable output. 50um processinguid jet (E.coli function extract) within the vesicle, which leads to, (4) a visuallyplasmid detectable output (Figure 1 right). In order to reconnect with more traditional biology Eva Eva takes advantage of the interaction with physicists also works on two other model organisms20x confocal whenever andc engineers in Dan Fletcher’s laboratory. This mix of there is time. One project investigatesmicroscopy the questions of on expertise recently led to the development of a technique vesicle continuedwith on page 3 The Adolph C. and Mary Sprague Miller Institute for Basic Research in Science University of California, Berkeley GFP expressedPage 2 100um from within Figure 2: Generation of giant unilamellar vesicles (GUVs) by microuidic jetting. Analogous to blowing soap bubbles we generate large vesicles by deforming a planar bilayer with a technology typically found in an inkjet printerhead. (a) To enable communication between ‘inside’ and ‘outside’ of the vesicle we need to be able to incorporate transmembrane (TM) proteins into the synthetic lipid bilayer. The incorporated proteins are made visible through fusion to Green Fluoresecent Protein (GFP). (b) We encapsulate an E.coli protein expression system, which allows us to express proteins inside the vesicle. (c) Light microscopy image of a vesicle made by this technique. 2010 Miller Senior Fellowship Announced The Miller Institute is pleased to name Physics Profes- American Association for the Advancement of Science sor Saul Perlmutter the 2010 Miller Senior Fellow for and is a member of the American Academy of Arts and a five-year term beginning July 1, 2010. Sciences as well as the National Academy of Sciences. He received his PhD from UC Berkeley in 1986 work- Professor’s Perlmutter uses astrophysical measurements ing under Richard Muller (Miller Professor 1990). to probe the make-up and evolution of our Universe. This is demonstrated through his work on As the third Miller Senior Fellow named, supernovae, which has led to the discovery Perlmutter will join Randy Schekman, of a form of energy called “dark energy”. Professor of Molecular and Cell Biology, It is now believed that over 75% of the and Gabor Somorjai, Professor of Chemis- universe is made of dark energy; a finding try, as part of our community of world-re- that has revolutionized our scientific un- nown scientists. Taking its place alongside derstanding of the universe. Dark energy the Institute’s other programs: the Miller is widely acknowledged to be one of the Fellowships, the Miller Research

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