PHYSIOLOGICAL CAUSES AND CONSEQUENCES OF GENOME INSTABILITY

Guest: Dr. Graeme Hewitt, CRUK RadNet Jr Group Leader

Graeme Hewitt is a Cancer Research UK RadNet Junior Group Leader at King's College London's Comprehensive Cancer Centre. Graeme received his PhD in 2016 and was awarded the Newcastle University Medical Sciences Doctoral Thesis Prize for his work investigating the interplay between the protein degradation pathway autophagy and DNA double strand break (DSB) repair. Graeme then completed postdoctoral research at the Francis Crick Institute in London, UK in the lab of Simon Boulton. During this time, Graeme was seconded to Artios pharma, Cambridge, UK where he developed cell-based target engagement, and high-throughput cell-based assays for compound screening for novel DDR targets. Graeme is an expert in DDR mechanisms and their application in cancer treatment. His research has uncovered detailed regulatory and engagement mechanisms of the oncogenic chromatin remodeler ALC1/CHD1L. Furthermore, Graeme identified ALC1 as a possible therapeutic target in ATM- and HRD-deficient cancers. In 2021, Graeme was awarded a CRUK RadNet fellowship to begin an independent research programme to investigate targeting the DDR in conjunction with radiotherapy. The Hewitt lab uses whole genome CRISPR screens, proteomics and a wide range of cell-based assays to identify and characterise novel genetic dependencies. 

trainer: Max Moenikes

In the pursuit of gender equality and equal opportunities in science, effective communication plays a pivotal role. This workshop is designed to empower individuals, with a particular focus on promoting and advancing women in science, by enhancing their rhetorical and communicative skills. In academic and professional settings, individuals often encounter speaking engagements ranging from team meetings and conferences to thesis presentations, funding applications, and teaching roles. While these opportunities can be exciting, they may also evoke feelings of stage fright and stress. However, with proper practice and preparation, anyone can confidently navigate these situations. In this seminar, we aim to cultivate essential rhetorical skills in a practical and engaging manner, recognizing the unique challenges faced by women in science. Our primary objective is to foster harmonious interactions among body language, voice, and content, enabling participants to authentically embody their intentions and garner approval from their audience.

The seminar curriculum is structured around the three fundamental pillars of rhetoric:

1) Body Language: Participants will learn to leverage posture, gestures, facial expressions, and eye contact for effective communication, creating a confident and impactful presence

2) Voice: Emphasis will be placed on techniques such as breathing, volume control, intonation and articulation, enabling participants to amplify their voices and convey their messages with clarity

3) Content: Strategies for structuring and planning speeches, as well as mastering argumentation techniques, will be explored, empowering participants to articulate their ideas persuasively

"ADP-ribosylation at the nuclear pore complex", (FOR5504-associated group leader)

"Metabolic deregulation, genome instability, and the progression of chronic kidney disease", (project 8)

Our data suggest that the accumulation of unresolved DNA damage is linked to metabolic changes that may, in a vicious cycle, drive further genome instability, chronic kindey disease (CKD) progression, and kidney fibrosis. This project is expected to further substantiate this link and present potential strategies for future tissue-protective strategies with the ultimate long-term goal to confirm these findings in samples from patients and to develop strategies for future clinical applications. 

"Unravelling the role of RPA4 in genome stability using the naked mole-rat physiology.", (FOR5504 - start-up funded postdoc)

The similarities between human replication protein A complex (RPA4) and naked mole rat (NMR) RPA4 (hgRPA) (62% protein identity) make the NMR an intriguing model for investigating aRPA function in vitro and in vivo. The RPA4 single-stranded DNA binding and winged-helix domains are also present in NMR (Ensembl and NCBI). Studying RPA4 in NMR could provide valuable insights into its contribution to genome stability, potentially shedding light on the remarkable healthspan and longevity of this unique rodent species.

Hence, with my independent project I aim to study three major points: 

• Are RPA4 and aRPA forming a functional complex in the naked mole-rat, in a tissue-specific manner?
  • Determine RPA expression in different NMR tissues 
  • Determine whether aRPA complex exists in tissues highly expressing RPA
• Is the naked mole-rat aRPA involved in the DNA damage response (DDR)?
  • Study the RPA4 function in a context of DNA damage in vitro using NMR primary cells and in vivo.
• Does hgRPA4 enhance genome stability in mouse? 

Guest: Dr. Michael Klutstein, The Chromatin and Aging Research Lab (CARL), The Hebrew University of Jerusalem

Our lab is interested in understanding the process of epigenetic aging. We are mainly interested in aging in the reproduction system (oocytes and sperm), and the oral immune system. We also investigate the processes which occur in cells due to a changing environment such as occurs with the aging process. We combine genomic tools and various molecular techniques as well as live cell imaging in our studies. We take advantage of several model systems- including cell lines, mice and yeast in our experiments, and also study samples from the clinic to show the clinical relevance of our findings

Annual Meeting of the DGDR:

DNA Repair Meeting 2024

https://dgdr6.webnode.page/l/annual-dgdr-meeting/

September 25-27 | Cologne, Germany

Registration Deadline 30.6.24

Registration: :https://cms2.vcongress.de/dgdr-2024

"Mechanism and consequences of SLX4IP- and ERCC1-XPF-dependent telomere dysfunction", (project 6)

The objectives of this research proposal are to understand how SLX4IP regulates ERCC1-XPF function to ensure telomere stability and to elucidate the physiological consequences of a dysfunctional SLX4IP-ERCC1-XPF module, particularly with regards to telomere stability, general genome stability and kidney homeostasis.