Real-time dynamics of mutagenesis
...reveal the chronology of DNA repair and damage tolerance responses in single cells.
Bad luck and mutations
Stochastic DNA damage response causes cell-to-cell mutation rate variation.
Single-molecule DNA repair in live bacteria
Using photoactivated single-molecule tracking to directly follow individual DNA repair proteins in living E. coli cells.
Methods for single-molecule imaging
Custom single-molecule fluorescence microscopes, imaging methods, and software.
Bacterial DNA Repair and Mutagenesis
Bacteria have a remarkable capacity to thrive in adverse environments. Their adaptability relies on stress responses that provide temporary protection, for example by repairing cell damage or removing toxic chemicals. Such phenotypic adaptation offers cells a window of opportunity to evolve permanent stress resistance through genetic change. Failures to cure bacterial infections with antibiotics are often due to stress responses that promote bacterial survival as well as the evolution of drug resistance. Our lab seeks to understand how this works at the molecular level using a quantitative interdisciplinary approach. We focus on the mechanisms of DNA repair and mutagenesis, which are essential both for stress survival and for genetic change. A key aspect of our research is developing fluorescence microscopy techniques to visualise molecular events in real-time within living cells. We use super-resolution microscopy and single-molecule tracking to record the localization and movement of individual molecules such as DNA repair enzymes or transcription factors. To monitor the cellular responses to stress, we use microfluidic devices for imaging single cells. This allows us to decipher how molecular events inside cells determine long-term cell fates. Curiously, single-cell analysis revealed that bacterial phenotypes are variable even in a constant environment, a phenomenon that may be linked to stress survival. We discovered that mutation rates are also variable due to fluctuations in the expression of DNA repair proteins. These findings open fundamental questions about the mechanisms and regulation of mutagenesis, which we are now addressing using a range of novel microscopy and genetic approaches.
Uphoff Lab | Department of Biochemistry | University of Oxford
News
Upcoming conferences and seminar talks
Seminar at University of Leicester - 26th June 2019
Joao Ferreira Fernandes
May 2019
Joao has come to the lab for a rotation project in his D.Phil programme on Infection, Immunology, and Translational Medicine.
Aditya Jalin
May 2019
Aditya has won a summer vacation studentship from the Biochemical Society for a project in our lab.
Poster Prize
April 2019
Valentine Lagage won a Best Poster Prize at the UK RNA Polymerase Workshop. Congratulations!
Maxence Vincent
May 2019
Welcome to Maxence Vincent who joins our group with a postdoctoral fellowship from the Human Frontiers Science Programme.
Colworth Medal
April 2019
Stephan Uphoff will receive the 2020 Colworth Medal from the Biochemical Society
Just published
November 2018
Choosing the right label for single-molecule tracking in live bacteria: Side-by-side comparison of photoactivatable fluorescent protein and Halo tag dyes is now published in the Journal of Applied Physics D. Well done Nehir and Jarno!
Biochemical Society Prize for Emma Jones
July 2018
Emma Jones has been awarded a Biochemical Society Prize in recognition of her research project and contribution to the lab. Many congratulations!
New article published
June 2018
Real-time dynamics of mutagenesis reveal the chronology of DNA repair and damage tolerance responses in single cells, in PNAS. See also the commentary by Bennett van Houten and Neil Kad.
May 2018
Special Edition of Current Opinion in Microbiology co-edited with Ariane Briegel.
Preprint
March 2019
Does gene expression noise jeopardize DNA damage signaling? A mathematical model together with stochastic simulations and single-cell imaging provide some answers: biorxiv doi.org/10.1101/551911.
Under the Lens
September 2018
We started a journal club with a bunch of groups at Oxford, where we take recent papers on Microbial Imaging "Under the Lens". This goes together with a new regular feature in Nature Reviews Microbiology. The first one is on "Filming flagella and pili in action". More details can be found here.
Welcome to new students
September 2018
Three new students are joining our group this autumn: Lois Ogunlana - Interdisciplinary Bioscience DTP programme - jointly supervised with Craig McLean in Zoology. Madeleine Hooper - Biochemistry Part II student. Mayisha Sultana - exchange student from Princeton.
Oxford Conference: Single Molecule Bacteriology
9-12 September 2018
We co-organized the 84th Biochemical Society Harden Conference on Single Molecule Bacteriology.