Featured News from the Lab
Measuring cellular responses to PARP inhibition
Our newest paper on PARP inhibitor toxicity has been published in Nature Communications! Have a look how high-content imaging reveals the earliest cellular responses to PARP inhibition and unravels the sequence of events from PARP trapping to DNA damage, cell cycle arrest and cell death. Here you can access the complete article and browse through the Editors' Highlights, or read the UZH/EurekAlert public releases.
Analysis of PARP inhibitor toxicity by multidimensional fluorescence microscopy reveals mechanisms of sensitivity and resistance
Exploiting the full potential of anti-cancer drugs necessitates a detailed understanding of their cytotoxic effects. While standard omics approaches are limited to cell population averages, emerging single cell techniques currently lack throughput and are not applicable for compound screens. Here, we employed a versatile and sensitive high-content microscopy-based approach to overcome these limitations and quantify multiple parameters of cytotoxicity at the single cell level and in a cell cycle resolved manner. Applied to PARP inhibitors (PARPi) this approach revealed an S-phase-specific DNA damage response after only 15 min, quantitatively differentiated responses to several clinically important PARPi, allowed for cell cycle resolved analyses of PARP trapping, and predicted conditions of PARPi hypersensitivity and resistance. The approach illuminates cellular mechanisms of drug synergism and, through a targeted multivariate screen, could identify a functional interaction between PARPi olaparib and NEDD8/SCF inhibition, which we show is dependent on PARP1 and linked to PARP1 trapping.
Approach of the lab featured in BIOspektrum
Our research and experimental approach was recently featured in a High Content Imaging (HCI) Special in BIOspektrum, the magazine of the German bioscience societies GBM, VAAM, GfG and DGPT. Have a look at the current issue, HCI is not only about large-scale screens. Here is the article and here the link to the complete issue.
Lab research featured in UZH Magazin and in the Annual Report 2017
Research of the group brought to life by Roland Fischer and photographer Marc Latzel for UZH Magazin 01/2018 (UZH News). Download the full article or the complete magazine (in German). Read the English translation here.
Our work was also included in the UZH Annual Report 2017. Download the complete Annual Report or have a look at the online summary.
News & Views: Daughters sense their mother's stress
Read the News & Views article on our recently published work on the effects of DNA damage propagation from one cell generation to the next. It nicely puts our work into context with recent findings from the labs of Tobias Meyer, Sabrina Spencer, and Chris Bakal. Access the News & Views via PubMed or the Cell Cycle homepage.