2 year postdoc position available
How do bacterial defense systems such as CRISPR-Cas impact the spread of conjugative plasmids?
Molecular Systems Biology, Department of Cell and Molecular Biology, Uppsala University, Sweden.
A two-year position on a Carl Tryggers postdoc stipend is available to undertake single-cell studies of the effect of bacterial immune systems on conjugative plasmid spread with Dr. Daniel Jones at Uppsala University.
Project description: Mobile genetic elements (MGEs) such as phages and conjugative plasmids play a key role in enabling bacteria to adapt to new ecological niches. At the same time, recent work has begun to illuminate the breadth and diversity of bacterial defense systems against MGEs. In particular, the protein players in CRISPR-Cas systems have been the subject of intensive biophysical investigation into mechanisms of target search and specific target recognition. For instance, we have previously shown that the well-known Cas9 effector protein takes approximately six hours to locate a specific DNA target in Escherichia coli .
In this project we aim to connect these biophysical observations with the population dynamics of conjugative plasmid spread at the single-cell level. Given the slow search times observed for CRISPR-Cas effector proteins, how much do these systems need to be expressed in order to provide effective protection, and what is the cost to the cells of doing so? Does cell-to-cell variability in CRISPR-Cas expression affect the vulnerability of the populations to MGE invasion? To address these questions we perform time-lapse fluorescence microscopy on populations of donor and recipient cells, grown in microfluidic devices. By labeling the molecular players (e.g. conjugative plasmids, CRISPR-Cas proteins) with fluorescent tags, we can directly observe individual conjugation and interference events in quasi-real-time. Advanced techniques in quantitative image analysis allow us to compile these individual events into a comprehensive picture of the balance between conjugation, interference, and the cost of immunity.
Requirements: Applicants should possess a PhD degree in biophysics, systems biology, microbiology, microbial ecology, or a related field, as well as general molecular biology laboratory skills. Strong computational/quantitative skills are important, and experience in quantitative image analysis is a plus. Candidates must have received their PhD from an institute other than the Department of Cell and Molecular Biology at Uppsala University and cannot currently have employment at the Department of Cell and Molecular Biology. Proficiency in spoken and written English is required.
Application: Please submit your CV, a letter describing your research interests and skills, and contact information for two references to Daniel Jones (firstname.lastname@example.org), Department of Cell and Molecular Biology, Biomedicinskt centrum, Husargatan 3, 752 37 Uppsala, Sweden. Applications will be evaluated continuously until a suitable candidate has been identified.
Starting Date: As soon as possible.
Additional info: The Biomedical Center offers a superb interdisciplinary working environment located just outside of central Uppsala. Uppsala is located 40 minutes north of Stockholm by train, 20 minutes from Stockholm’s international airport.
 Jones DL, Leroy P, Unoson C, Fange D, Ćurić V, Lawson MJ, Elf J. Kinetics of dCas9 target search in Escherichia coli. Science. 2017 Sep 29;357(6358):1420-1424.