Roger Brent received a BA in Computer Science and Mathematics from the University of Southern Mississippi in 1973, where he applied AI techniques to protein folding. He earned his Ph.D. in Biochemistry and Molecular Biology from Harvard University in 1982 for studies with Mark Ptashne. As a graduate student, he showed that the E. coli lexA gene repressed genes involved in the response to radiation damage, cloned the gene, produced and purified its protein product using and sometimes augmenting the new developed recombinant DNA methods, and studied binding of the repressor to its operators, showing that its differential binding affinity for these sites affected the timing of the response. As a postdoctoral fellow with Mark Ptashne, he tested a number of ideas about the mechanism of transcription regulation in yeast by using the prokaryotic LexA protein and in subsequent experiments creating chimeric proteins that carried LexA fused to activators native to yeast. These "domain swap" experiments established the modular nature of eukaryotic transcription regulators.
In 1985, Brent became a Professor at Massachusetts General Hospital and Harvard Medical School in the Department of Genetics. There, he and his coworkers used yeast transcription that depended on chimeric DNA-bound proteins as a genetic probe for protein function in higher organisms. This work contributed to the development of two-hybrid methods, to the ability to scale them up via interaction mating, and development of protein interaction methods and peptide aptamers to learn more about function via making and breaking interactions. Perhaps as important as the actual technologies was the coeval development of ideology (e.g. doctrine) for using protein interactions to make valid inferences about biological function.
In the late 1990s, Brent worked with Sydney Brenner to start the lab for the Molecular Sciences Institute in Berkeley, California. In 1998, Brent joined MSI as its Associate Director of Research. He became Director of Research in 2000, and President and CEO in 2001. At MSI, he and his coworkers began long term work to understand the quantitative function of a paradigmatic cell signaling system in budding yeast. This work revealed the existence of hitherto unsuspected persistent physiological states that affect signaling and gene expression. In 2009, he joined Fred Hutchinson Cancer Research Center as a Member in the Division of Basic Sciences and extended his research program to signaling systems in cells in animal tissues. This research has revealed additional physiological states. Consequences of cell-to-cell differences in these states include differences in complex outcomes for the organism including the impact of pre-existing mutations and lifespan.
Brent accepted appointments in the UCSF Department of Bioengineering and Therapeutic Sciences in 2001, the UW Genome Sciences Department in 2010, and the UW Bioengineering Department in 2014. In 2001, he was named a senior scholar of the Ellison Medical Foundation. In 2003, with Stanley Fields, he was awarded the Gabbaye Prize for his contributions to the development of two-hybrid methods. Brent was elected a fellow of the AAAS in 2011 for "contributions in the area of biochemistry, transcription, genomics and systems biology".
In parallel to his academic work, Brent helped found and works on (1987-2014) Current Protocols, a series of "how to clone it" and other lab manuals, accessed by more than three million scientists worldwide. He served on the SAB of American Home Products (Genetics Institute/Wyeth Ayerst Research), chaired SABs for several smaller companies, and does significant ad hoc consulting work. He is an inventor on 11 issued and several pending US Patents. He runs a pilot project, Center for Biological Futures (2011-2014) that works with social scientists and other scholars to better understand the impacts that developments in biology are having on human affairs. For some years he has carried out advisory work aimed at helping diminish the probability of biological attack and at taking advantage of other more positive impacts of developments in biology and related sciences.
My research is in the interdisciplinary field of systems biology. This field combines physics, chemistry, and biology methods to investigate organization within biological systems, on size scales that typically range from a few proteins to many cells. Results are yielding insights into how the highly structured macroscopic world of living organisms is built from the stochastic microscopic world of individual molecules. They are also providing an improved conceptual foundation for medical and biotechnology developments, with impacts on topics such as drug discovery, personalized medicine, biofuel generation, and bioremediation. My research projects include:
Algorithm development for cell modeling
Computer simulations are used in systems biology as a way to build intuition about the system dynamics, to test hypotheses, to make predictions, and to identify essential system components. I am developing modeling tools that can simulate biochemical systems with a relatively high level of detail, in which individual molecules are represented with nanometer-scale spatial resolution, but that are also fast enough to allow the simulation of tens of thousands of molecules over several minutes of real time. I developed algorithms for simulating reactions between freely diffusing molecules in solution and for interactions between molecules and surfaces. These algorithms are implemented in the Smoldyn computer program, which can be downloaded from the Software page. My current algorithm development addresses the detailed simulation of cytoskeletal filaments and membranes.
Biological cells are highly crowded spaces, with often 20-30% of the volume occupied by macromolecules such as proteins and nucleic acids. This fact has been both known and investigated for many years, but there remains no predictive theory for how much crowding slows diffusion, nor for the quantitative effects of crowding on biochemical reaction rates. Using a combination of analytical theory and computer simulation, I am developing semi-emipirical theories to address these questions. If successful, these theories will allow in vitro measurements of biochemical reaction rates to be converted to in vivo reaction rates, for the appropriate native biological systems. This will help address a major problem of cell biology modeling, applicable to both conceptual and computational models, which is that the quantitative data on intracellular biochemical reaction rates is generally very sparse.
Cell signaling in yeast
The yeast mating pheromone response pathway is a classic model system for studying intracellular signaling because it is relatively easy to study, is similar to many mammalian signaling pathways, and is a rich system. In collaboration with other scientists at the Molecular Sciences Institute, I am using analytical and computational methods to investigate information transfer along the pathway. This study addresses topics such as the effects of biochemical feedback and feedforward on information transfer and the importance of having aligned dose-response curves at different points of the signaling network.
Mechanics and dynamics of the bacterial cytoskeleton
The bacterial cytoskeleton is highly dynamic. For example, the MinC, MinD, and MinE proteins of E. coli exhibit a remarkable oscillation between the cell poles: the MinD protein polymerizes in a helical coil that extends from one pole towards the cell center, is depolymerized by MinE, forms a new polymer from the opposite pole, and so on. In another example, the FtsZ protein forms a central ring around the cell center that constricts during cell division to yield two daughter cells. In recent work, I investigated how the micron-scale shapes of these cytoskeletal polymers might arise from mechanical forces between individual proteins, along with how these polymers are likely to apply forces to cell walls. While I am not continuing to focus on this research direction at the moment, I plan to return to it in a year or two, equipped with simulation methods that can simultaneously model chemical reactions, filaments, and membrane dynamics. This cell division system has been extensively modeled in the past, but it continues to reveal new insights and to be an ideal model system for exploring biochemical spatio-temporal dynamics.
Gaymon helped found and helps steer the Center for Biological Futures, where he is a senior research fellow. He holds a PhD in Cultural Anthropology from UC Berkeley and a PhD in Systematic Theology from the Graduate Theological Union. Gaymon’s PhD thesis in anthropology, Biofabrication: Experience and Experiments in Sciences and Ethics, provides an account of the ethical, affective, and scientific price to be paid for working within “synthetic biology.” His PhD thesis in theology, On the Care of Human Dignity, provides a critical analysis of how the figure of human dignity has become integral to ecclesial, political, and ethical thought and practice. Gaymon is co-author of Sacred Cells?: Why Christians Should Support Stem Cell Research and co-editor of The Evolution of Evil and Bridging Science and Religion.
Gaymon has conducted intensive experiments in how to design practices and venues needed for facilitating effectual inquiry into and engagement with contemporary biology. He is a Principal of the Anthropological Research on the Contemporary and a founding co-designer of the Human Practices experiment at the Synthetic Biology Engineering Research Center (SynBERC), a joint project of Berkeley, MIT, Harvard, UCSF, and Stanford. He led Human Practices at the International Open Facility Advancing Biotechnology (BIOFAB) at LBNL and UC Berkeley, and was a research fellow of the Center for Theology and the Natural Sciences at the Graduate Theological Union, Berkeley. His design work emphasizes collaborative and multi-sited empirical inquiry, a shift of emphasis from theory to disciplined concept work, and sustained attention to the micro-politics of knowledge production.
Gaymon uses the anthropological techniques of participant-observation to examine the purposes and rationales forming scientific activities and organizations today. His work is informed by the Greek concept of eudaemonia, sometimes translated as “flourishing.” His research asks to what extent the sciences are contributing to human flourishing, and, where they are not, what should or can be done?
This inquiry is oriented by a number of interrelated questions: How are new scientific objects (careers, modes of expertise, institutions, biological systems) brought into the world, named, and circulated? What capabilities must scientists and those working with scientists form in order to bring this about? How has scientific invention come to be framed and elaborated as “salvational,” that is, uniquely capable of saving lives, economies, and ecosystems? Finally, and crucially, what qualifies scientists and those working with them to think and act ethically and critically in relation to these framings of biological work?
At the CBF, Gaymon is developing three research projects. The Ethical Figure of Global Biotechnology will inquire into ethical framings of relations among bioengineering, global health, sustainability, and biosecurity; how these framings specify promises and dangers; and how they are currently being unsettled. Biology and the Ethics of Biosecurity will investigate how attempts to separate bioethics and biosecurity over the past 30 years have limited the modes through which ethical truth claims and capacities can be advanced. Biology and the Question of Pastoral Power will examine how religious denominations and organizations in the U.S. have responded to developments in biology, and how this has reconfigured the governance of science as well as the politics of religious practice.
Additionally, Gaymon is helping develop two projects in support of ethics pedagogy and critique. Ethical Equipment for Contemporary Science studies the habits, dispositions, and virtues needed to produce scientific work and capacities. One of its outputs will be a repertoire of ethics pedagogy modules formulated as guides to conducting inquiry and shaping its ramifications. Reconstructing the Sciences, developed in collaboration with the Anthropology Research Collaboratory at UC Berkeley, will provide an online critique of pressing questions, unresolved problems, and blind spots that accompany the drive of ambitious scientists and engineers to accumulate and consolidate the funding and status required for a competitive mode of operation.
Alex received a BS in microbiology (2000) and an MS in geosciences (2002) from Texas A&M University. As an undergraduate, he worked in Bill Park’s laboratory on projects to alter starch properties of rice using recombinant technology and DNA-marker-assisted selective breeding techniques. In his master's program, he developed science education tools for high school teachers and earned an NSF science education certificate. He also interned and then worked as an environmental consultant on soil and groundwater contaminant transport and fate.
Alex began a PhD program at the University of North Texas in 2003 in the laboratory of Pam Padilla, where he investigated genetic and physiological mechanisms by which C. elegans survive anoxia. He showed that most glycolysis enzymes are not required for adult anoxia survival, but that a glyceraldehyde-3-phosphate dehydrogenase isoform is both necessary for wild-type anoxia survival behavior (continued motility) and sufficient to extend anoxia survival. Alex and colleagues later found that C. elegans males, as well as hermaphrodites with chemically or genetically reduced ovulation rates, displayed enhanced anoxia survival.
Alex joined Tom Johnson’s lab as a postdoc in 2008 to work on a path opened by Rea et al. (2005) involving the expression levels of a reporter gene for a small heatshock protein, hsp-16.2. The work was enabled by use of transgenic animals containing a reporter that fused the promoter for hsp-16.2 to the coding sequence for green fluorescent protein (GFP). This reporter was variably expressed in isogenic populations of C. elegans. Animals that expressed more of the transgene lived longer and were more thermotolerant. These experiments thus identified a quantitative biomarker whose high value in early adulthood defined a physiological state correlated with longevity. Alex investigated whether the variation in reporter expression might be due to the fact that the original transgene was a multicopy array or a function of locus. He did this by comparing the lifespan prediction powers of the original, multicopy transgene to two newer version of the same promoter-GFP fusion placed as a single copy at a defined locus on a different chromosome. Lifespan prediction power was not a function of locus or copy number and Alex published that in 2012.
Additionally, in different mutant backgrounds, Alex has observed a compression of physiological states toward either bright, long-lived states or dim, short-lived states. These observations provide evidence of genetic control of worm-to-worm differences in gene expression, and indicate that not all the variation in the population is purely stochastic. Genes that increase the amount of differences in gene expression in a population may help ensure that individuals are in different physiological states and can thus respond differently to selective pressure, an idea expressed by George Martin and others.
In the Brent Lab, Alex has continued work to dissect the sources of biological variation that cause worm-to-worm differences in gene expression. He has quantified variation in gene expression attributable to experimentally tractable biological events. He has been able to do this by using 21st century reporter gene technology and by adopting the approach taken by Colman-Lerner et al in 2005 to dissect sources of variation in gene expression in yeast, and reformulating that to work in C. elegans. He has initiated an experimental program to enable quantification of cell-to-cell and worm-to-worm variation in key metazoan signaling systems in specific cells of C. elegans throughout developmental time. Such work may define additional physiological states important for multicellular animals. This work has recently been funded by a K99 grant awarded to Dr. Mendenhall by the National Institute on Aging at NIH.
Roger and Alex have recently published a manuscript that compares the expression of single copy and a multicopy reporters of hsp-16.2 in all the cells of the intestine. In doing so, Alex and Roger have developed a method for precisely measuring reporter expression at cell resolution in all the cells in a live metazoan tissue.
Click here to view the publication.
Alex has recently written a review with Roger and Monical Driscoll on using measures of single cell physiology to understand organismic aging that will be published soon. Alex and Roger are also working on other manuscripts reporting mechanisms of animal-to-animal and cell-to-cell variation in gene expression and other complex quantitative traits.
James Redfield is a PhD student in Religious Studies at Stanford University and is currently with the Center for Biological Futures at the Hutchinson Center.
James received a BA in Comparative Literature in 2006 from Dartmouth College. Supported by grants from Dartmouth and the J.S. Dickey Center, he conducted research in Morocco, Turkey, Germany, and France resulting in an interview and essay on Franco-Algerian author Leïla Sebbar, published in 2008.
James was a German Academic Exchange Service scholar at the Freie Universität Berlin from 2006 to 2007 and a research fellow in the project “Tension” at Berlin’s Institute for Cultural Inquiry (ICI) from 2007 to 2008. Also in Berlin, he worked as a research assistant at the Max Planck Institute for the History of Science and as a freelance translator, photographer, and writer, with an article published in the Berlin newspaper die tageszeitung. With Mimma Congedo from the ICI Berlin, he is co-editing Reflections on Images (Zurich: Olms Verlag). Following his work in Berlin, James was awarded (and declined) a Fulbright scholarship, instead accepting a graduate fellowship at UC Berkeley and receiving an MA in anthropology in 2010. He conducted field research on Zen Buddhism from 2008 to 2010 resulting in an essay that will be published in the multilingual journal Diogenes/la revue Diogène. At Berkeley he also deepened his study of Judaism and decided to continue his graduate training in this field.James’ current work focuses on Jewish ethics, as understood through textual traditions in the original ancient and modern languages. At the Hutchinson Center, he is analyzing the relevance of these religious traditions to contemporary bioethical problems. In particular, he is concerned with how Jewish thinkers can speak to the emerging ethical challenges posed by new developments in biological knowledge and capability. His working papers focus on the relation between revealed scripture, human interpretation, and the creation or stewardship of life.
Meg Stalcup received her PhD from the Joint Program in Medical Anthropology at UC Berkeley and San Francisco. Her work, in biology, science communication and anthropology, has consistently bridged disciplines, and she is actively engaged in developing forms and practices of collaboration.
Since 2009 she has been laying the groundwork with colleagues for the Center for Biological Futures, launched in October 2011.
Meg has designed and executed several independent multi-year studies. Each drew on and developed methodology in the interpretive human sciences. Her masters thesis described the ethnobotany of plants used medicinally and ritually, obtained from an urban market in Rio de Janeiro. Her doctoral research involved four years of fieldwork on the politics of security in the United States and at Interpol, in France. Subsequently, she engaged in a year-long collaborative follow-up investigation into counterterrorism training for state and local law enforcement in the United States. Her work generally utilizes qualitative interviews with stakeholders, detailed description (from people to funding sources, governance and regulatory structures, and the pertinent legal apparatus), and concept work requiring historical contextualization and adaptation of concepts from philosophy.
Meg continues her work in security, and is also currently working on several projects in global health that aim to provide insight into how metrics function both as forms of knowledge production and governance. She is especially interested in approaches to the persistent quandary of how to best allocate financial and human resources in health systems, specifically in terms of delivering basic interventions.
Meg previously obtained a BS in Biology from UC San Diego and an MS in Biological Sciences from the Federal University of Rio de Janeiro. She completed the UC Santa Cruz program in Science Communication in 2001, and has produced illustrations for the California Academy of Sciences, the American Museum of Natural History, McGraw-Hill, Anthropology Today, and the UC Berkeley Graphics Department, among others. She has received fellowships from the Brazilian National Research Council (CNPq), the IGCC Public Policy and Biological Threats Training Program, the UCHRI Seminar in Experimental Critical Theory, UC Santa Cruz, UC Berkeley, and the US National Science Foundation.
Bill received a BS in physics  from the University of Minnesota. As an undergraduate, he worked in Laurence J. Cahill’s laboratory, managing and participating in the building of a rocket payload to measure the electrodynamic properties of the auroral ionosphere. The payload (ARCS4) flew successfully in 1991.
Bill began a PhD program at the University of New Hampshire in 1989 in the laboratory of Roy Torbert, where built and calibrated charged particle detectors to study plasma physics in several contexts, including the auroral ionosphere, a barium release experiment, and an artificial HF heating experiment. In the latter context, he showed that the nonlinear ponderomotive force, an unavoidable driver of currents, present whenever an electromagnetic wave has an intensity gradient, most likely drives the formation of cavity structures in plasmas, not only at previously predicted and observed meter scales, but also at scales ranging from tens of meters to tens of kilometers. He was a NASA Graduate Student Fellow from 1992-1995.
Bill joined the UC Berkeley Space Sciences lab as a postdoc in 1996 to work on results from the FAST (Fast Auroral SnapshoT) spacecraft, a polar orbiter with extremely high burst-mode resolution, configurable on-orbit. He built a database of all auroral overflights by FAST, indexed by probable traversals of field-aligned auroral current sheets. Bill implemented and deployed the software to extract these traversals from the raw magnetometer data. He used this database to index and explore other aspects of the enormous FAST data set. For example, he discovered that the energetic electrons in upgoing electron beam (UEB) events have a greater spatial inhomogeneity than their downgoing counterparts, a clear signature of two distinct acceleration mechanisms for these two populations.
In 2002, he began to apply his overarching interest in the organizing principles of complex systems to the study of living cells. In 2005, he began to research the idea that macromolecules ought to produce detectable acoustic radiation, or ultrasound, when undergoing conformational changes or binding, and he began the quest to detect such sounds. He holds a patent on the use of sound and an apparatus to detect these conformational changes (US8402828 B2).
In 2006, Bill began work as a research scientist in the laboratory of Geoffrey Loftus, at the Department of Cognitive Psychology at the University of Washington. Here he contributed to the study of the human visual memory system, designing and implementing experiments with human subjects. In his experiments, he presented to human participants series of visual stimuli, for varying controlled durations ranging from 17 ms to 537 ms, to human participants. The stimuli were grayscale images of human faces and naturalistic scenes. After the stimuli, participants were asked questions testing their memory of the stimuli. The better the performance, the stronger the memory. Bill discovered that, rather than increasing, for example, linearly with increasing duration of stimulus, that the strength of memory formation appeared to follow a power law. Bill then presented participants with different pictures of the same scene comprised of either low frequency or high frequency spatial information, which the mammalian brain(cat, Enroth-Cugell and Robson, 1966 and primate, Schiller et al., 1976) process in different locations. He found that such exposure to images of different spatial frequency bands was more effective in forming memories than presentation of those same figures with pure low frequency bands and pure high frequency bands, and that the effect of presentation of both kinds of stimuli was more than additive.
In 2011, Bill arrived at the laboratory of Roger Brent, where he works on physical and computational approaches to the study of cell signaling. He has contributed to continual improvements in microscopy, data analysis and modeling, and understanding of the structure of cell signaling systems.
Enroth-Cugell, C, and Robson, J. G The contrast sensitivity of retinal ganglion cells of the cat. J Physiol. 1966 Dec;187(3):517-52
P. H. Schiller, P. H., Finlay, B. L. and Volman, S. F.. Quantitative studies of single-cell properties in monkey striate cortex. III. Spatial frequency. Journal of Neurophysiology 39, 1334-1351 (1976)
Bryan received a B. S. in biology from Roger Williams University in Rhode Island, an MLA in biology from Harvard extension school in Cambridge, Massachusetts. He first worked at Biogen Idec, in Cambridge, Massachusetts, where he was a member of the genomic group in the discovery biology department headed by John McCoy, and where he attended Harvard at night. At Biogen Idec, he designed and built recombinant DNA constructions and made numerous recombinant cell lines in support of research (target validation and screening) for therapeutics against cancer and neurodegenerative diseases. This work involved developing new cloning and cell culture methods (including new vectors and cell lines) as well as establishing within the group methods published elsewhere. In 2004 he moved to Seattle to work with Jean Feagin at the Seattle Biomedical Research Institute on the molecular biology of the malaria parasite, Plasmodium falciparum . There, he led work that helped identify all the ribosomal proteins in this organism and contributed to studies of its RNA splicing. In specific, he developed 5' and 3' RACE methods to identify the unusual, fragmented Plasmodium rRNAs, and developed a recombinant assay to detect RNA splicing by activation of luciferase expression. His work there required him to help establish in Seattle, for the first time, recently described means to transfect the parasite with recombinant constructs, and to train numerous other Seattle researchers in these methods to assist their participation in the Gates Foundation Malaria Vaccine Initiative. In 2009 he moved to Jim Kublin's lab at FHCRC as lab manager and continued his work on malaria. There, he developed means to optimize the in vitro production of mosquito stages of P. falciparum including means to produce gametocytes and ookinetes. For his Master's thesis at Harvard, he used recently developed technology based on the use of the Bxb1 bacteriophage integrase to engineer new Plasmodium reporter lines to test means of producing genetically attenuated whole-cell vaccine candidates in vitro.
In 2011, Bryan came to the Brent lab as a Research Scientist and lab manager. Bryan's main work here has been on technology development to better quantify the operation of signaling and gene expression systems inside cells in C. elegans and in S. cerevisiae. This work has required the development of new fluorescent reporter proteins, for example, with altered fluorescent lifetimes (Sands et al. 2014). It has also required development of increasingly powerful means to assemble complex DNA constructions inside cells, and at scale. Bryan will be publishing this work soon and is currently working on an automated version of the system. Bryan has recently submitted a review of high throughput DNA assembly technologies (Current Protocols in Molecular Biology, accepted) which will become a useful guide to any researcher interested in efficient means to assemble complex DNAs.
Bryan believes that biological knowledge and capability should be applied to helping people. To that end, he has worked as a volunteer medical technologist at Primeros Pasos, a nonprofit public health clinic in Xela Guatemala. He later worked with educators and social workers in Cusco, Peru to set up and conduct an intestinal parasite screening program for children there.
1. Mi, S., Lee, X., Shao Z., Thill G., Ji B., Relton R., Levesque M., Allaire N., Perrin S., Sands B., Crowell T., Cate R. L., McCoy. J. M. and Pepinsky, R B. (2004). Lingo-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nature Neuroscience 7:221-228.
2. Sands, B., and Feagin J. E. Plasmodium falciparum mitochondrial ribosomal proteins. Abstract presented at the 2006 Molecular Parasitology Meeting, Woods Hole, Masschusetts.
3. Feagin, J. E., Harrell, M. I., Lee, J. C., Coe, K. J., Sands, B., Cannone, J. J., Tami, G., Schnare, M. N. and Gutell, R. R. The fragmented mitochondrial ribosomal RNAs of Plasmodium falciparum. (2012) Plos One (7) 6: e38320.
4. Sands, B.; Jenkins, P., Peria, W.J.; Naivar, M.; Houston, J.P.; Brent, R. (2014). Measuring and sorting cell populations expressing isospectral fluorescent proteins with different fluorescence lifetimes. PLOS One.
5. Sands, B. and Brent, R. (2015). Review of post Cohen-Boyer methods for single segment cloning and for multisegment DNA assembly. Current Protocols in Molecular Biology (accepted, to be published Nov/Dec 2015)