Research positions in systems biology of cell signaling

To this end, the lab seeks a number of exceptional and exceptionally motivated research fellows.

How to apply.

Researchers  interested in applying for positions should write Roger Brent or Julie Ngo.  Their initial communication should include a CV and a cover letter explaining how their work is relevant to the work of the lab, describe the scientific ambitions of the applicant, and describing how possible joint work would help applicant develop intellectually and achieve those ambitions. 

 

For research positions, applicants who wish serious consideration should be prepared to cause to be sent three (or more) thoughtful letters of recommendation.  Such letters should be from people who know the applicant and think well of their work.  Letters should describe the applicant, and how (and how well) the person applying for the position thinks and works.  Letters should state, in the opinion of the person writing the letter, why postdoctoral study in the lab makes sense for the applicant, how the lab could support the applicant's scientific and intellectual development, and how the researcher and their work will benefit the scientific goals of the lab.  It is helpful but not essential that the persons writing the letters be known to Brent and others at the FHCRC.

For internships, applicants who wish serious consideration should write, describing their ambitions for future development, their research experience, how their experience to date might qualify them to work in this lab, and how work in this lab in particular will contribute to their future development.  Applicants should attach to this cover letter a copy of their undergraduate transcripts, and cause to be sent a letter from one or more of their advisors in university.  The letter of recommendation should speak to the above issues.

Experimental biology fellows.  Lab seeks motivated and talented research fellows with successful graduate and/or postdoctoral experience in molecular, cellular, or developmental biology.  Experience with yeast genetics and/or single cell measurements a plus. Fellows will work as part of a multidiscipinary biological research team.  Team is seeking to discover deeper truths about how cells sense external information, transmit it internally, and (ultimately) operate upon that information to make decisions.  This work is deeply grounded in careful directed experimentation on a prototypical or archetypical cell signaling system, the pheromone response system in Saccharomyces cerevisiae.  Fellow must be a talented and dedicated experimentalist, and must have evidenced this by performing significant work as a graduate student and/or postdoc as reflected in important papers. Fellow must have real interest in participating in and eventually, leading, work that makes a significant contribution to scientific understanding. Fellow will join and continue to develop a research program of genetically-enabled quantitative physiological experimentation to understand information handling by this system.  Because work will require working with researchers who are not veteran biologists (for example, fellows trained in experimental physics) the biology fellow should be articulate and willing to teach, must be unafraid to talk about concepts from math and physics, and must be numerate.  Moreover, fellow must (obviously) have an interest in learning to work across these disciplinary boundaries to address important problems in biology.

Experimental physicist(s).  Lab seeks research fellow with successful graduate and/or postdoctoral experience in (for example) high energy physics or condensed matter physics.  Fellow(s) will work as part of a multidiscipinary biological research team.  Team is seeking to discover deeper truths about how cells sense external information, transmit it internally, and (ultimately) operate upon that information to make decisions. This work is deeply grounded in careful directed experimentation on a prototypical or archetypical cell signaling system.  Fellow will continue the development and use of optical microscopic (image cytometric) and flow cytometric methods to quantify molecular events needed for signaling in single cells.  Fellow must be a talented and dedicated experimentalist, and will have evidence this by performing significant work as a graduate student that made use of mathematical and computer skills.  Fellow must obviously have an interest in applying background and mindset from experimental physics to this set of important biological problems.  Fellow must also have an interest in, by their work, making a significant contribution to human understanding.   Fellow thus must have real interest in learning about contemporary biology and the tools the team brings to bear on the problem, including in particular learning about the experimental system under study and genetic manipulations.

Experimental physicist(s)/ computational biophysicist(s) in biological simulation.  Lab seeks research fellow with successful PhD and/or postdoctoral experience in experimental physics, computational biophysics, and/or the use of simulations to solve physical problems. Fellow(s) will work as part of a multidiscipinary biological research team.  Team is seeking to discover deeper truths about how cells sense external information, transmit it internally, and (ultimately) operate upon that information to make decisions.   This work is deeply grounded in careful, directed experimentation on a prototypical or archetypical cell signaling system.  One tool for learning about these systems is the use of spatially accurate, particle based, stochastic simulations of the chemical reactions among proteins that cell signaling systems use for their operations, including the Smoldyn 2.0 simulation package.  Fellow must work with existing simulations and develop new ones to ask and answer questions suggested from experiment.  Fellow must have performed significant work as a graduate student that extended scientific understanding and evidenced mathematical and computer skills.  Fellow must obviously have an interest in applying background and mindset from this work to biology, including this set of important biological problems, and, must intend, by their work, to make a significant contribution to human understanding.   Fellow thus must have real interest in learning about contemporary biology and the tools the team brings to bear on the problem, including in particular learning about the experimental system under study and genetic manipulations.

Research fellow in computational biology. Lab seeks research fellow with significant programming ability to lead development of biological simulation software. Fellow(s) will work as part of a multidiscipinary biological research team.  Team is seeking to discover deeper truths about how cells sense external information, transmit it internally, and (ultimately) operate upon that information to make decisions.   This work is deeply grounded in careful, directed experimentation on a prototypical or archetypical cell signaling system.  One tool for learning about these systems is the use of spatially accurate, particle based, stochastic simulations of the chemical reactions among proteins that cell signaling systems use for their operations, including the Smoldyn 2.0 simulation package.   Fellow will lead further development of Smoldyn.   In particular, fellow will further develop Smoldyn to make it SBML compatible, and will lead development of new biological functionalities such as those pertinent to gene regulation and to aspects of cell signaling systems.  Fellow may lead development of Smoldyn into a module that can run within other laboratory or systems biology environments such as Virtual Cell, MatLab, SBW.   Fellow must have experience in research environments and have a strong physical science background (if a biologist, that means comfort with biophysics and some physical chemistry).  Fellow should also have thorough knowledge of C and C++, be willing and able to work with an existing base of C code, and have some experience with computer graphics. Experience with Python, Subversion, AutoTools, MatLab, Sourceforge, and Unix, experience in merging existing, artistic talent/ aesthetic sense, experience with multi-threaded programming, and professional or professional level academic programming experience.

Programmer/ moviemaker.  Lab seeks programmer with experience in Renderman to turn output of simulations of intracellular processes running in Smoldyn 2.0 into explorable animated movies.  Person could be undergraduate student, graduate student, or intern.

Student internships. We will consider applications for a very limited number of student internships from recent university undergraduates.

Background

At the Hutch, the lab will continue to pursue work made possible by the Alpha project (2002-2009) at MSI.  That work began as an attempt to devise means to enable construction of a mechanism-based, quantitative model of the Saccharomyces cerevisiae pheromone response system.   The idea was that attainment of a model that could accurately predict the quantitative behaviors of the system in response to defined perturbations would be "tantamount to understanding".  The further hope was that the quest to build such a predictive model would require us to bring into being new experimental and computational methods of broad application, and would result in a better understanding of how to conduct research into other biological problems that required interdisciplinary work of this type. 

 

Although we made a great deal of progress toward these goals, the project did not succeed in reaching the large goal of a predictive model, nor do we believe that this goal will be achievable much before 2020.

Careful experimental and computational work did, however, reveal numerous quantitative behaviors of the model yeast cell signaling system which are fundamental in the sense that they are widely conserved in cell signaling systems in higher eukaryotes.  Many of these "systems level" quantitative cell signaling behaviors are only revealed after careful single cell physiological experimentation.  Their study continues to be tractable to a combination of this experimentation, forward genetics, directed genetics, and "deep proteomic" mass spectrometry to reveal sites on proteins that make up the system that regulate its behavior. 

This continued study of key quantitative behaviors in model signaling systems will be the focus of the new lab.

In addition, the lab will contain an explicit experimental social science component. During the next decades, progress in molecular biology, cell biology, developmental biology, neuroscience, genomic biology, and systems biology, will have profound impact on our world.  This increase in knowledge and capability will have consequences for human security, conceptions of human identity, human interaction with the economically important living world, and the human interaction with the rest of the natural world. Interested lab members will be encouraged to learn to think broadly and carefully about the impacts that continued increases in knowledge and capability in biology are having on human affairs, and about their own role in these processes. The lab will work to facilitate interactions with individuals and organizations in Seattle and the rest of the world to enable its members to better understand and influence these developments. .