Friday, 7 July 11:00am – 12:00pm

This seminar will be delivered in Chemistry Lecture Theatre 4 and Online (Zoom) Please email chemistry.researchsupport@sydney.edu.au for zoom link and password.

Speaker: Prof. Katherine Franz, Duke University

Host: Prof. Elizabeth New

Title: Why is copper toxic, and how can we direct it for benefit?

Abstract: Normal and pathogenic cells require a menu of metal nutrients for optimal growth, but also strategies to mitigate toxicity associated with misregulated or excessive levels of metals, including copper. Cells adjust copper homeostasis mechanisms depending on cell type, local growth conditions, and in response to stress. These situations present opportunities to manipulate cellular copper as a therapeutic strategy against several diseases, including cancer and infection. But what are the targets and mechanisms of copper toxicity? Here I will present new approaches to interrogate cellular proteomes for protein targets of copper overload. By combining conventional protein expression level analysis with measurements of protein folding stability changes across a cellular proteome, our data reveal proteins involved in multiple biological processes that are directly disrupted by changes in copper status induced by pharmacological manipulation.^{1, 2} More broadly in the context of infectious diseases, we are using these and other approaches to explore how cellular responses at the metallomic and proteomic level affect and are   affected by microbial susceptibility and adaptation to antimicrobial treatment.

References

1- Wiebelhaus, N.; Zaengle-Barone, J. M.; Hwang, K. K.; Franz, K. J.; Fitzgerald, M. C. Protein

Folding Stability Changes Across the Proteome Reveal Targets of Cu Toxicity in E. coli. ACS

Chemical Biology 2021, 16, 214-224.

2- 2. Robison, A. T. R.; Sturrock, G. R.; Zaengle-Barone, J. M.; Wiebelhaus, N.; Dharani, A.;

Williams, I. G.; Fitzgerald, M. C.; Franz, K. J. Analysis of copper-induced protein precipitation

across the E. coli proteome. Metallomics 2023, 15, mfac098.

Click here for more details about the Hans Freeman Lectureship and our guest speaker for 2023, Professor Katherine Franz.