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In situ single-molecule imaging of the bacterial DNA damage response & The role of H3K4 methyltransferase Setd1a in the small intestine

CMCB PhD/Postdoc Seminar

Date:17.05.2019, 16:00 - 17:00
Speaker: Leonard Schärfen, Neha Goveas
Location: CRTD, auditorium left
Host: Prof. Michael Schlierf, Prof. Francis Stewart

Speakers: Michael Schlierf, Leonard Schärfen (Predoc)

Title: In situ single-molecule imaging of the bacterial DNA damage response

Abstract: Emergence of antibiotic resistance among pathogenic bacteria remains a major challenge in modern medicine. As novel targets for antibiotic development become scarce, recent efforts have focused on understanding and preventing the rapid evolution towards resistance. One of the key mechanisms driving mutation and adaptation associated with antibiotic stress and DNA damage is the SOS response. This regulatory circuit is well characterized but lacks a global understanding due to its many inputs and nuanced mechanisms of regulation. The transcriptional repressor LexA is the central factor, controlling expression of over 40 genes with functions such as DNA repair or mutagenesis.

Through tagging of the chromosomal lexA gene in Escherichia coli, we can follow the diffusion of individual LexA proteins using single-molecule tracking photoactivated localization microscopy (smtPALM) in living cells. We identify DNA-bound and mobile transcription factor populations and directly measure the SOS response intensity following antibiotic stress. Supplementing our dynamic live-cell data, we obtain PALM images of fixed cells in order to precisely quantify the number of LexA molecules under various conditions. The single-molecule resolution in combination with genetic and environmental perturbations allow us to draw conclusions on the overall regulatory behavior of the intricate genetic network, as well as state and abundancy of LexA during weak and strong responses to DNA damage.

Speakers: Francis Stewart, Neha Goveas (Predoc)

Title: The role of H3K4 methyltransferase Setd1a in the small intestine

Abstract: The small intestine is a rapidly proliferating tissue maintained by intestinal stem cells (ISCs), which generate transit-amplifying cells that differentiate into absorptive and secretory cell lineages. Canonical Wnt signaling regulates ISC maintenance and the well-defined epithelial hierarchy. Our studies using conditional mutagenesis in mice and organoids, suggest a crucial relationship between Setd1a and Wnt/ß-catenin signaling.

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