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“We are made from DNA. We can create more with DNA”, Simon Shiu, intern at Institut Pasteur in Paris

Simon Shiu is currently completing a research internship at the Institut Pasteur Department of Structural Biology & Chemistry under the supervision of Dr Marcel Hollenstein.He shared with us his insights after spending one month working in the lab!

Simon Shiu is a postdoctoral students in in Prof. Julian Tanner’s lab (see his profile for more information). His research interest lies in imagining and designing novel DNA structures. His current project focuses on da-Vinci inspired DNA polyhedra for targeted drug delivery, diagnostics and bioelectronics.

What is your training background? I found my research interest in my undergraduate final year project where I studied G-quadruplex nanowire. It gave me the first experience in imagining the folding of DNA in 3D and since then I loved it. After my undergraduate studies, I returned to Hong Kong from the UK for master research where I had a chance to work on the complement cytosine-rich i-motif. It showed me the diverse possibilities from just four bases of DNA and made me curious on what more one can create with DNA. I then joined Prof. Tanner’s lab for PhD study. Together with his expertise on aptamers that’s also made of DNA, I was able to create several designs for diagnostic purposes to replace expensive and unstable antibody-based methods. At the end of my PhD, I developed my own theory on designing DNA nanostructures and published it as a concept. With that experience, I decided to move on designing DNA nanostructures for therapeutics. Why did you choose the Institut Pasteur Department of Structural Biology & Chemistry with Dr Marcel Hollenstein for this research internship? Dr. Marcel Hollenstein is a renowned expert in nucleic acid chemistries. His expertise will be particularly useful for the application of DNA nanostructures in therapeutics or targeted drug delivery. Chemically modified DNA will have very high resistance towards degradation in the physiological condition. One of the objectives here is to find out the suitable modification on DNA for our new nanostructures. Also, we are trying to use the Cryo-electron microscope in Pasteur to solve the 3D structure of new nanostructure design. From the internship, I will gain the experience in Cryo-EM and be able to continue the project when HKU has the same facility. Can you tell us a little bit more about what you are doing on a daily basis at the laboratory? The diverse culture here in Pasteur and Dr. Hollenstein’s group allow me to work at my own pace as in Hong Kong. When I come to the lab, I usually start the experiment planned the day before and spend some time updating myself with literature or thinking about new designs when I am waiting for the result. Once I obtain the result, I will analyse it and see what lesson it is giving me to improve or ask the next research question. How this new research environment can contribute to developing your ongoing research project? With different expertise in research, I am constantly getting new insights from discussion with members in the research group to improve my work. Every day I am learning new knowledge and techniques that could help to better illustrate our ideas to the community. What has the most surprised you about this internship so far? Apart from the typical four bases of DNA, there could be so many different possible modifications on nucleic acids to create lots of possibilities on nanostructure design. Apart from the project, I can see the Eiffel Tower from the institute! Is there any upcoming step / event in the research internship you are looking forward to?

Training on Cryo-EM and collaboration on X-ray crystallography to reveal the 3D structure of novel design of DNA nanostructures. Also the discussion with new people everyday!


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