Lab Members

   Roger Brent | Steve Andrews | Gaymon Bennett | Alex Mendenhall | James Redfield
Meg Stalcup
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Roger Brent - PI   

Phone:
+1 (206) 667-1482

Email:
rbrent@fhcrc.org

 

 

Roger was born in Spartanburg, South Carolina in 1955. He received a BA in Computer Science and Mathematics from the University of Southern Mississippi in 1973, where he did some work attempting to apply AI techniques to protein folding. He went on to get a 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, also 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, Roger became a Professor at Massachusetts General Hospital and Harvard Medical School Department in the Department of Genetics. 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 widely used two-hybrid methods (1988-1993), to the ability to scale them up via interaction mating (1992-1994), and to the eventual development of protein interaction methods as a useful way to learn more about biological function. In parallel, Roger and his coworkers developed peptide aptamers as reverse "genetic" agents to study the function of proteins and allelic protein variants (1999-2001), and, more recently, as dominant forward "genetic" reagents to identify genes and pathway linkages in organisms, such as human cells, that are intractable to classical genetic analysis. (Perhaps as important as the actual technologies is the coeval development of ideology (e.g. doctrine) for using them.) This work is described in more than 90 research papers and reviews.

In parallel to his academic work, Roger is a longtime (since 1984) advisor to the biotech and pharmaceutical industries. He served on the SAB of American Home Products (Genetics Institute/Wyeth Ayerst Research), chairs scientific advisory boards for several smaller companies, and does significant ad hoc consulting work in genomics and computational biology. He is one of the founders (1987-2001) of Current Protocols, including Current Protocols in Molecular Biology, a "how to clone it" manual, which is updated every three months and has about 10,000 subscribing labs. He is founder and organizer (since 1994) of the "After the Genome" workshops. He is an inventor on 11 issued and several pending US Patents. Since the middle 1990s, he has exhorted and advised various bodies in the US and abroad on functional genomics and computational biology, including the National Institutes of Health, the Welcome Trust, the National Science Foundation, Department of Energy, Defense Advanced Research Projects Agency, and other parts of the US Defense Department.

Roger joined the Molecular Sciences Institute in 1998 as Associate Director. He was named Director in 2000 and President and CEO in 2001. Brent joined the faculty of UCSF Department of Biopharmaceutical Sciences as an Adjunct Professor in 2000 and was named a Senior Scholar of the Ellison Medical Foundation in 2001.  In 2009, Roger joined Fred Hutchinson Cancer Research Center as a Member in the Division of Basic Sciences.

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Steve Andrews - Staff Scientist   

Phone:
+1 (206) 667-7007

Email:
sandrews@fhcrc.org

Website:
http://www.smoldyn.org/andrews/index.html

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 deep 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.

Macromolecular crowding

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.

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Gaymon BennettGaymon Bennett - Senior Research Fellow   

gbennett@fhcrc.org

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.

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Alex MendenhallAlex Mendenhall - Postdoctoral Fellow (starting September 2011)   

Phone:
To be provided

Email:
amendenh@fhcrc.org

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 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 transcript levels of a small heatshock protein, hsp-16.2. The work was enabled by use of transgenic animals containing a transcriptional reporter, Phsp-16.2::gfp::unc-54. 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 variance might be due to where the transgene was located in the genome by examining the variance of different transgene constructs and different fluorescent protein derivatives in different places in the genome. He is preparing a paper on his comparison of the worm-to-worm and cell-to-cell variation and predictive powers of single copy and tandem array transgenes.

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 variance, and indicate that not all the variance in the population is purely stochastic. Genes that increase variance 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 will continue work to determine the cellular basis for worm-to-worm variance in Phsp-16.2 expression and how that variation affects lifespan. He will initiate an experimental program to enable quantification of cell-to-cell and worm-to-worm variance in key metazoan signaling systems in multiple cells of an organism throughout developmental time. Such work may define additional physiological states important for multicellular animals.

Dr. Mendenhall has produced a guide for caenorhabditis elegans Intestine Cell Identification (Version 1.3) available for download in PDF at the following link:

Caenorhabditis elegans Intestine Cell Identification Guide Version 1.3.

Purpose: To act as a general guide for C. elegans intestine cell identification in adult animals and to inform programmers as how to the human eye identifies nuclei in digital images of C. elegans intestine cells in order to design software for the autmoation of said process.

Please contact Dr. Mendenhall directly for questions or comments at amendenh@fhcrc.org or alexander.mendenhall@gmail.com

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James RedfieldJames Redfield - Researcher   

Phone:
NA

Email:
jredfiel@fhcrc.org

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.

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Meg Stalcup - Senior Research Fellow   

Phone:
+1 (206) 667-7158

Email:
mstalcup@fhcrc.org





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.

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