Lee Kong Chian Distinguished Professor Public Lecture by Shaw Prize and Kavli Prize Laureates

On 15 November 2024, the Institute of Advanced Studies (IAS) at Nanyang Technological University (NTU) hosted the Lee Kong Chian Distinguished Professor Public Lecture, featuring two eminent speakers: Prof Maria Jasin (Shaw Prize in Life Science and Medicine 2019) and Prof Virginijus Šikšnys (Kavli Prize in Nanoscience 2018). Sponsored by the Lee Foundation, the event was organised in conjunction with the IAS Frontiers Conference on Genome Engineering held at the School of Chemistry, Chemical Engineering, and Biotechnology (CCEB). Prof Nripan Mathews, Associate Director of IAS, warmly welcomed the guests and audience. This was followed by opening remarks from the Guest of Honour, Prof Chiba Shunsuke, Chair of CCEB, NTU.

[Top] From left: Prof Chiba Shunsuke, Assoc Prof Tan Meng How, Prof Virginijus Šikšnys, Prof Maria Jasin and Prof Nripan Mathews. [Bottom] (left) Prof Nripan Mathews delivering the welcome address, followed by Prof Chiba Shunsuke giving the opening remarks.

The public lecture explored two critical topics in genome engineering: the risks and opportunities of DNA editing and the dynamic interactions between bacteria and bacteriophages.

Editing Your DNA: What Could Possibly Go Wrong? by Prof Maria Jasin

Prof Maria Jasin, a leading biomedical researcher at the Memorial Sloan Kettering Cancer Center, delivered an insightful talk titled "Editing Your DNA: What Could Possibly Go Wrong?" CRISPR gene editing has revolutionised biomedical science, offering significant therapeutic opportunities for various medical contexts. However, the use of DNA double-strand breaks (DSBs) as part of the editing process introduces potential risks. Prof Jasin discussed how unintended consequences can arise from off-target effects, highlighting that the precision of editing is critical to minimise risks such as chromosomal rearrangements or tumorigenesis.

Prof Jasin's research focuses on understanding DNA recombination and its role in maintaining genomic integrity. She emphasised that homologous recombination (HR), a critical DNA repair mechanism, plays a major role in minimising the risk of errors during gene editing. Through detailed insights into DSB repair, she explained how the two primary pathways - homologous recombination and non-homologous end joining (NHEJ) - can lead to different outcomes, affecting genome stability. She highlighted how her lab's research aims to develop new methods of assessing and mitigating the risks associated with CRISPR-based editing, ensuring safer therapeutic applications.

Prof Maria Jasin's engaging lecture on DNA editing.

Her presentation also covered how engineered endonucleases such as I-SceI have provided valuable insights into DSB repair, with studies demonstrating the complexity of protein-DNA interactions involved. Prof Jasin further described how advanced approaches, including gene editing tools like TALENs, ZFNs, and CRISPR, have been utilised to introduce targeted DNA breaks at specific sites, each with unique advantages and challenges. A notable highlight was her discussion on the significance of tumor suppressor genes such as BRCA1 and BRCA2 in DNA repair, emphasising their role in maintaining genomic integrity and their implications for cancer predisposition.

An insightful Q&A with Prof Maria Jasin, moderated by Assoc Prof Tan Meng How (CCEB).

During the Q&A session,  some enthusiastic attendees asked about the potential unintended effects of gene editing, such as loss of heterozygosity (LOH) and chromosomal instability, and how these risks could be suppressed or mitigated. Prof Jasin provided insightful responses, focusing on the need for continued research to understand and manage these risks effectively.

Arms Race in the Bacterial World: Who is the Winner? by Prof Virginijus Šikšnys

Following Prof Jasin's talk, Prof Virginijus Šikšnys, a Distinguished Professor at Vilnius University, presented an interesting talk on "Arms Race in the Bacterial World: Who is the Winner?" Prof Šikšnys is known for his groundbreaking work on CRISPR-Cas systems, which have transformed genome-editing tools and applications. His talk focused on the ongoing evolutionary battle between bacteria and bacteriophages, the viruses that infect bacteria.

He explained how bacteriophages, as major parasites of bacteria, drive the development of sophisticated bacterial defense mechanisms. In response to viral attacks, bacteria have evolved a variety of defense strategies, including the CRISPR-Cas system. This system enables bacteria to "remember" past infections and target invading viral DNA for degradation. Prof Šikšnys discussed how this microbial arms race has spurred the evolution of both bacteria and bacteriophages, with phages evolving mechanisms to evade bacterial defenses and bacteria adapting new strategies in response.

Prof Virginijus Šikšnys' intriguing lecture on the ongoing evolutionary battle between bacteria and bacteriophages.

One of the key highlights of Prof Šikšnys's presentation was the demonstration of how understanding bacterial defense systems has enabled the development of powerful genome-editing tools. His pioneering research on Cas9 biochemistry laid the foundation for transforming CRISPR-Cas into a versatile tool for targeted DNA modification. He elaborated on the structure and molecular mechanisms of these bacterial immune systems, detailing how different components of the CRISPR-Cas machinery work together to provide adaptive immunity in bacteria.

Prof Šikšnys also touched upon the ethical and practical implications of utilising these tools in genome editing. He emphasised that while these technologies hold immense promise, careful consideration of their safety and ethical use is essential. His presentation concluded with an exploration of the future potential of bacterial defense mechanisms in advancing genome-editing technologies and other biotechnological applications.

A vibrant and interactive Q&A session with Prof  Šikšnys.

The lecture was followed a lively Q&A session, where attendees pondered on a wide range of topics such as the development of genome-editing technologies, and the intricate dynamics of bacterial defense systems. Prof Šikšnys provided insightful responses, emphasising the importance of understanding the underlying biology to advance the development of effective and safe genome-editing technologies.

Overall, the public lecture provided a fascinating glimpse into the cutting-edge research shaping the future of genetic engineering. From assessing the risks associated with DNA double-strand breaks to exploring the natural arms race between bacteria and bacteriophages, Professors Jasin and Šikšnys highlighted the promise and challenges of genome-editing technologies in a rapidly evolving field. Their talks underscored the critical role of basic research in driving innovations that could transform medicine, agriculture, and biotechnology in the years to come.

"Thoroughly enjoyed the speakers' reflections on their research journey, fun life stories, delights found in academic endeavours, and notions on reading out-of-domain papers as a side hobby."- Teng Yuxin (PhD student, IGP NTU)