How it all began...
Everything big starts with small steps. In 2020, our team chose a completely different track from previous years, going to the molecular tools in synthetic biology. This meant that we did not have academic support we have been enjoying for several years, and we need to explore lots of things ourselves. We want to share our experience with you and tell a story that, no matter how different your iGEM project is, you can always find like-minded people if you work with passion.
We had multiple meetings from our fellow HK iGEM team and Koc team, Cre mutant co-author- Dr. Eroshenko and the yeast expert - Dr. Karen Yuen. We also presented our project to all lab members in Prof JD Huang's lab.
We had meetings with HKUST and HKCityU team to discuss our projects and possible future
It was interesting to hear about what they are working on, and build connections even we cannot meet
face-to-face under the pandemic situation.
We also had a meeting with Koc team, in which we not only talked about our respective projects, but also gave advice on each other's projects. We also exchanged connections that we have, so we can approach respective personnel to improve our projects and reach out to more experts in the field. The COVID situation has definitely opened the door for more international collaborations!
Meeting Dr. Eroshenko
The inspiration behind our idea to achieve phenotypically heterogeneous monocultures of cells arose
the Brainbow system, that used an incredibly elegant approach of creating several phenotypes in one
of cells by using Cre recombinases. However, as we did more research, we realized that it was too
idealistic to assume that Cre would effortlessly invert the genetic sequence flanked by facing loxP
sites as we saw more papers talking about the high frequency of off-target events of the wild-type
and high frequency of deletions.
In order to find the solutions, we stumbled upon the paper published by one of the fathers of synthetic biology, George Church, who introduced and screened mutations of the Cre recombinase that improve the accuracy of the enzyme and reduce the chances of deletions. We talked about it more with Dr Eroshenko, one of the coauthors of the paper and now a co-founder and CSO at HelixNano. He gave us insightful feedback on our project’s designs and objectives. Based on his advice, we decided to try to use the Hin recombinase in the future, which is a natural invertase enzyme in Salmonella. Adding on that, we decided to implement a tighter control on the expression of phenotypes with the CRISPR array. Our construct will allow downregulation of the fluorescent protein expression once the phenotype is switched. Dr Eroshenko also gave us a nice application idea of our system: separating pathways for the production of toxic opioids. Metabolic pathway engineering It was truly inspiring talking to Dr. Eroshenko!
Meet Dr. Karen Yuen
In early project development stages, we interviewed Dr. Karen Yuen, since she is an expert in yeast
genome recombination and shuffling techniques. In the meeting, we also proposed several gene circuit
designs and gain valuable feedback on how to visualise and prove our result. Dr. Karen Yuen
suggested a very interesting approach, which is to draw all the graph before we actually design the
experiments so we would have an idea of what to achieve.
We also inquired about the use of the system in yeast cultures like bio-fermentation and productions, and Dr. Karen Yuen say it would be possible if the project is successful.
Presentation at Prof JD Huang's lab~
We were also lucky to have the opportunity to present to lab members in Prof JianDong Huang’s lab at
HKU. Prof Huang was the PI of HKU teams from 2007 to 2012. He is also renowned in the field of
biology, and his lab mostly works on designing artificial biological parts to attack cancer cells
prevent infectious diseases. We gained a number of valuable advice on our project. After the
not only learnt more about how to present our data more effectively, but also gained more ideas
potential applications of our project.
It was truly rewarding talking to so many scientists at one time!
We are going to meet Marcelo from Global Yeast on 28/10/2020.
Global Yeast works on advanced digital fermentation. We hope that our recombinase system may be able to help in the aspect of smart fermentation and industrial yeast strains, based on our work on moving towards a better understanding of cell metabolism & polygenic behaviour combined with the evaluation of process inputs to the sugar conversion capability into ethanol.
We hope that we can adjust the future direction of our project to be more oriented towards applications in real life, and we look forward to sharing our meeting with you in the Jamboree!
Learn more about Global Yeast: https://www.globalyeast.com/