CPLC Seminar: Gavin King "Single molecule measurements of topography and force reveal mechanisms underlying general secretory system activity"

10/19/2018 4:46:03 PM CPLC Staff

How are proteins transported across membranes? The general secretory (Sec) system of E. coli exports precursor proteins via a translocase comprising the peripheral ATPase SecA and the translocon, SecYEG. Precursor- and nucleotide-mediated structural changes of active translocases underlie the translocation process. Yet, determining mechanistic details of this complex system has proven to be challenging. The atomic force microscope (AFM) is well suited for imaging membrane proteins in near-native conditions and can achieve molecular-scale (~10 Å) lateral resolution coupled with ~1 Å vertical resolution (i.e., normal to the bilayer surface). We imaged individual translocases in lipid bilayers as a function of precursor protein species, nucleotide species, and stage of translocation. Topography results showed that starting from nearly identical initial states, active translocases evolve to exhibit precursor-dependent conformations at the plateau stage of activity. These data, acquired in near-native bilayers, suggest that the translocation mechanism varies with precursor species, a result that is not accounted for in conventional models of translocation. In addition to imaging, AFM can be used in force spectroscopy mode, providing access to energy landscapes. Our laboratory has developed precision AFM-based force spectroscopy techniques and applied them to study a peptide-lipid interaction that is essential to Sec system activity. Together with analytical modeling and simulations, the results represent a step towards a more detailed understanding of the export process in E coli., and more generally, of the stochastic kinetic pathways driving peptide-lipid interactions. 


1/24/2014 The Climate Corporation

The Climate Corporation (San Francisco, Seattle)
Our mission is to help all the world's people and businesses manage and adapt to climate change. We use a combination of weather monitoring, agronomic modeling, and weather simulation to provide real-time pricing and purchasing of customizable weather insurance to farmers in the United States.

Climate's technical staff numbers around 80, and we're hiring interns and full-time employees across many teams as we expand efforts on a new class of decision support tools for growers
(see http://goo.gl/e2uu9v).

Work is split across groups focusing on web applications for farmers and agents, risk and insurance policy management, internal platform and data services, and scientific modeling and research.

Intern & Full-Time Openings in the following areas:
1. Software engineering generalists with solid CS fundamentals, particularly anyone interested in building
(i) entirely new, large-scale distributed data services for scientific computing (we use Clojure); and (ii) web applications (Rails, Python, Javascript, and iOS) used by farmers to manage weather risk.

2. Quantitative researchers in statistics/ML, stochastic optimization, remote sensing, atmospheric physics, and agronomics. Our goal is to forecast statistical distributions of crop yield for any piece of arable land, synthesizing satellite images, digital elevation models, weather data, agricultural statistics, and geological surveys into multiscale models that underlie our data services.

3. Product Managers, and Designers to pull all this together into a compelling product.
The scale and interdisciplinary nature of the work drive a lot of cross-collaboration within the company, supported by a pressing need to build durable solutions to some very important problems.

The usual details about these positions are here: