Uphoff Lab website

I joined New College as a tutorial fellow in Biochemistry in 2021. I see myself as an interdisciplinary scientist, applying tools and approaches from across the natural sciences to understand fundamental biological processes. I studied physics as an undergraduate in Göttingen and came to Oxford for an MSc and a DPhil in biophysics. After a period of postdoctoral research in the field of systems biology at Harvard Medical School, I returned to Oxford where I lead a research group in the Biochemistry Department. I previously held a Research Fellowship at Jesus College, and a Junior Research Fellowship at St John’s College.

Teaching

I tutor undergraduate students at New College on a range of topics in Biochemistry. I lecture for the Biochemistry undergraduate course and the Doctoral Training Programme, and supervise research projects of Part II and graduate students in the Biochemistry Department.

Research Interests

Research in the Uphoff group focuses on DNA repair and mutagenesis in bacterial cells. We develop single-molecule imaging approaches to visualise DNA repair mechanisms and mutation events in real-time within individual living cells and we apply microfluidic devices to monitor cell behaviour over time. We integrate these measurements using quantitative data analysis and modelling to uncover how DNA repair and mutation dynamics support the short-term survival and the long-term genetic adaptation of cells that experience stress conditions.

Our research focuses on bacteria. Beyond their usefulness as tractable model organisms to study fundamental mechanisms that are conserved between prokaryotic and eukaryotic cells, bacteria play crucial roles in human health and the environment. Bacterial infections and rising antibiotic resistance are major burdens to society, impacting millions of lives and causing significant economic loss worldwide. The mechanisms of DNA repair and mutagenesis are at the core of bacterial cells’ ability to survive and adapt to antibiotics and our immune defences. I find it fascinating that we can now “see” the relevant molecules in action under the microscope.

Selected Publications

• Single-molecule imaging of LexA degradation in Escherichia coli elucidates regulatory mechanisms and heterogeneity of the SOS response; Jones EC, Uphoff S; Nature Microbiology 6, 981-990 (2021)
• Transient non-specific DNA binding dominates the target search of bacterial DNA-binding proteins; Stracy M, Schweizer J, Sherratt DJ, Kapanidis A, Uphoff S, Lesterlin C; Molecular Cell 81, 1-16 (2021)
• Bacterial phenotypic heterogeneity in DNA repair and mutagenesis; Vincent M, Uphoff S; Biochemical Society Transactions BST20190364 (2020)
• A quantitative model explains single-cell dynamics of the adaptive response in Escherichia coli; Uphoff S; Biophysical Journal 117, 1156-1165 (2019)
• Real-time dynamics of mutagenesis reveal the chronology of DNA repair and damage tolerance responses in single cells; Uphoff S; Proc Natl Acad Sci USA 115, E6516-E6525 (2018)
• Single-molecule analysis of bacterial DNA repair and mutagenesis; Uphoff S, Sherratt DJ; Annual Reviews of Biophysics, 46, 411-432 (2017)
• Stochastic activation of a DNA damage response causes cell-to-cell mutation rate variation; Uphoff S, Lord ND, Potvin-Trottier L, Okumus B, Sherratt DJ, Paulsson J; Science, 27290, 1094-1097 (2016)