Irma Querques is a Group Leader and Assistant Professor at the Max Perutz Labs, University of Vienna. She earned her master's degree in biotechnology from the University of Bologna and completed a joint Ph.D. at the University of Heidelberg and EMBL in 2018. During her Ph.D. with Dr. Orsolya Barabas, she developed a novel Sleeping Beauty transposon system for CAR T therapies. In 2019 she joined the laboratory of Prof. Martin Jinek at the University of Zurich as a recipient of a Branco Weiss, FEBS, EMBO and UZH postdoctoral fellowships. There, she has been at the forefront of investigating RNA-guided CRISPR-associated transposons, paving the way for utilizing these systems as programmable gene insertion tools. In 2023, she established her research laboratory, focusing on the mechanisms, functions and applications of transposons, with support from an ERC Starting Grant. 

How do bacteria transfer genetic information using transposons? How to utilize this knowledge to enhance gene transfer technologies?

During my postdoctoral work, we employed an integrative structure-function approach to investigate type V CRISPR-associated transposons (CASTs), renowned for their RNA-guided DNA integration and potential for programmable gene insertion in genome editing. Focusing on the CRISPR-Cas12k complex and the TnsC protein filament, we examined guide RNA organization, DNA targeting, and strategies for RNA minimization. 

Building upon these insights, we further delved into the structural mechanisms underlying RNA-mediated DNA insertion in type V CASTs. Our investigations revealed an unprecedented interaction between the CRISPR machinery and the ribosomal protein S15. We identified a novel moonlighting role of S15 in prokaryotic biology, beyond its traditional involvement in ribosome assembly, establishing it as an essential regulatory component of type V CASTs. This discovery had significant implications for genome editing, culminating in the successful reconstitution of these systems in human cells, marking a revolutionary advancement toward next-generation tools for targeted DNA integration.

Phong Nguyen completed a Bachelor in Biomedical Science at the University of Melbourne, Australia. His honours year was spent in Professor Rodney Dilley’s lab where he developed methods to improve engineered cardiac tissue. He then joined Professor Peter Curie’s lab at the Australian Regenerative Medicine Institute, Monash University for his PhD. During this time, Phong used the zebrafish to examine how muscle stem cells developed and contributed to growth and regeneration. For his postdoc, he moved to The Netherlands and joined Professor Jeroen Bakkers’ lab at the Hubrecht Institute to study how the adult zebrafish heart regenerates. In June, Phong moved to Paris to start his own group at the Institut Curie. He will continue to look into the regenerative capacity in the zebrafish heart.

The zebrafish can robustly regenerate its heart following injury. This is driven by the surviving endogenous cardiomyocytes being able to dedifferentiate, re-activate proliferation and generate new cardiomyocytes. Successful methods to induce proliferation have been intensively studied. However, the control of proliferation as well as how de novo cardiomyocytes redifferentiate and mature in order to integrate with the surrounding myocardium remains unclear. My research examined calcium handling dynamics and found a gene called Lrrc10, a regulator of calcium acted as a negative regulator of proliferation and induced maturation. Lrrc10’s dual function was also conserved in human iPSC-derived cardiomyocytes and mouse cardiomyocytes. Human iPSC-derived cardiomyocytes are commonly used for cell-based therapies, disease modelling and drug screens. However, their embryonic-like characteristics limits their use to fully recapitulate the adult human context. My research provides insights into the mechanisms required to induce cells to a more mature state and can have the potential to produce cell models that better represent adult cardiomyocytes.