How could CRISPR-Cas9 accelerate our discovery of treatments for genetic brain disorders?

In this episode, we take a look at how AAV-Perturb-Seq can change the way scientists study genetic disorders affecting the brain and other organs. Using adeno-associated viruses (AAVs) to deliver guide-RNA libraries for CRISPR-Cas9, this technique can help us understand complex conditions like 22q11.2 deletion syndrome and potentially uncover underlying disease mechanisms at single-cell resolution.

Antonio Santinha is a postdoctoral researcher at the D-BSSE of ETH Zurich in Basel, Switzerland, where he continues leading work combining CRISPR and single-cell omics techniques to study brain disorders.

Read the paper on AAV-Perturb-Seq:

Santinha, A.J., Klingler, E., Kuhn, M. et al. Transcriptional linkage analysis with in vivo AAV-Perturb-seq. Nature 622, 367–375 (2023). https://doi.org/10.1038/s41586-023-06570-y

Introduction: to min. 16:00

In the realm of genome editing, Cas9 enzyme is a versatile tool, guided by RNA to precisely cleave DNA at specific sites. Cryo-electron microscopy structures of Streptococcus pyogenes Cas9 unveil the intricate process of target DNA binding, guiding us through the essential stages of hybridization, activation, and conformational changes that illuminate the mechanism underlying this transformative technology. In a recent study, exploration of Cas9's intricate dynamics, revealed through 19 structures bound to both on- and off-target DNAs, uncovers how Cas9 identifies off-target sites. This revelations hold promise towards unlocking the full potential of genome editing. Furthermore, insights into de novo protein design open doors to a realm of possibilities, where customized proteins could be tailored to tackle intricate biological challenges, revolutionizing fields such as medicine, biotechnology, and beyond.

Martin Pacesa is a postdoctoral researcher at the École polytechnique fédérale de Lausanne (EPFL), situated by the picturesque shores of Lake Geneva in Switzerland. As a real CRISPR enthusiast, he has made numerous significant contributions to the field of CRISPR research.

Introduction: to min. 9:00

CRISPR: min. 9:00-23:00

Computational protein design: from min. 23:00 to end.

CRISPR is like the bodyguard of bacteria, protecting them against invaders like viruses. Some nomadic pieces of DNA have figured out how to use this system to move themselves around. In a recent study published in Cell, Michael Schmitz from the Lab of Martin Jinek at the University of Zurich (Switzerland) shed light on the structural basis for how this Type V CRISPR-associated transposon complex assembles. Learn how the host cell's ribosomal subunit kept the team awake at night and why structural biology is more relevant than ever in the age of alphafold2.

Hello world. In this episode, I introduce myself as the host of the new CRISPRli podcast on genome editing and beyond. My name is Kim, PhD student at ETH Zurich and the University of Zurich in Switzerland.

Based in Zurich, a hub for scientific research and innovation, our podcast features interviews with leading experts in the field of genome editing, including researchers and industry professionals. We'll discuss the latest breakthroughs and applications of genome editing tools, as well as their potential implications.

Whether you're a scientist, a student, or just someone curious about the cutting-edge of genetic research, CRISPRli is the podcast for you. Tune in and join the conversation about one of the most exciting and controversial technologies of our time.