Genome Integrity
The Genome Integrity Unit investigates how cells maintain their DNA health with specific interests in cancer and early development.
Research Overview
Our genome is an instruction manual that guides biological activity. When our genetic code is disrupted this can have serious health consequences. To maintain healthy DNA our cells have evolved specific mechanisms to protect the genome. This includes arranging the DNA into proper chromosomal structures, ensuring the DNA is accurately replicated each time the cell divides, scanning DNA for damage, and when necessary promoting DNA repair. If these functions are compromised the genome can become damaged. Cells with unstable genomes often choose to die to prevent potential negative consequences. However, if cells with unhealthy DNA continue to proliferate, this may promote cancer. Because cancers often display damaged or unstable genomes, this presents a therapeutic opportunity to specifically target and kill tumour cells.
We are specifically interested in understanding:
- How the ends of chromosomes, called “telomeres”, contribute to maintaining DNA health.
- How cells ensure the DNA is accurately replicated during the cell division process.
- How embryonic stem cells cope with the extraordinary demands on genome health during early development.
- How we can kill cancer cells by targeting unstable genomes.
Lab Head
Professor Anthony (Tony) Cesare is Head of the Genome Integrity Unit at CMRI.
Team Members
Research Projects
Telomere biology
We identified that telomere-loops (t-loops) function specifically to regulate ATM activity at human and mouse telomeres and collaborated with the Boulton Lab from the Crick Institute to identify how t-loops are resolved during S-phase to enable telomere replication. We are currently working to decipher the cell-cycle dependent telomere proteome and determine how t-loops are resolved in mitosis during non-canonical telomere deprotection.
DNA replication
We identified that nuclear actin polymerization alters nuclear architecture and promotes replication stress repair and characterized the regulatory pathway. Research in our lab continues to study how nuclear and chromatin architecture is regulated during DNA replication to promote genome stability. Additionally, we collaborate with Patrick Tam and the CMRI Embryology Unit to study the unique properties of replication in rapidly dividing embryonic stem cells.
Cell Death
Our studies of telomere biology and DNA replication led us unexpectedly to identify how lethal replication stress induces cell death specifically during mitosis through a pathway of cohesion fatigue and non-canonical telomere deprotection. We have expanded this study through collaboration with the Sydney West Radiation Oncology Network to focus on mechanisms of cell death in response to chemotherapeutic and radiation-oncology intervention.
Team Photos
Lab Alumni
Pragathi Masamsetti – Research Officer, CMRI with Patrick Tamm
Ronnie Low – Marie Skłodowska-Curie Actions Postdoc Fellow, Crick Institute with Simon Boulton
Patrick Stalder – Ph.D. Student ETH Zürich Institute of Molecular Systems Biology with Paola Picotti
Jessie Zhang – Medical Doctor
Ka Sin (Cassie) Mak - Regulatory Affairs Associate, MSD Pharmaceuticals
Sonja Frolich – Post-doctoral scientist University of Adelaide Research Centre for Infection Diseases, Danny Wilson Laboratory
Tara Bartolec – Ph.D. student UNSW with Marc Wilkins
Garima Moudgil – Medical Student, University of Queensland
Noa Lamm – Head of the CMRI Nuclear Dynamics Group
Georgia Kafer – Senior Lecturer, University of the Sunshine Coast
Sonja Frolich – Lecturer, The University of Adelaide
David Van Ly – Medical doctor
Sam Rogers – Senior Manager, Medical Affairs and Engagement
Cassie Mak – Senior Regulatory Affairs Associate (Jansen)
Anna Gonzalez Manjon - Scientific Project Developer, Kilian Jornet Foundation
Lea Cavalli – PhD student, Harvard University
Hannah Loh – Medical doctor
Antonia Blackwell – Lead Conservation Program Manager – North Head Sanctuary, NSW
Sienna Casolin – Research Assistant, U of Wollongong
Blake Lane – Research Assistant, CMRI
Publications
View Full Publication list.
The Genome Integrity Unit has published in Nature and other top journals.