Team:ZJU-China/Notebook/Brainstorm

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Notebook | Brainstorm

Rainbofilm

Our project
Gut Flora

Health & Medicine
Alternative Splicing
New application
week4
week5
week6

Rainbofilm

Biofilm has been our team’s long-standing interest. Though our motivation to study biofilm at first is on its effective elimination, a review paper on biofilm totally changed our view of it and led us into a new direction. When something as difficult to eliminate and natural as biofilm is, can we make use of it instead of destroying it? Following this strand of thought, we started to investigate the advantages brought by the advent of biofilm for the bacteria, such as its increased resistance to harsh conditions under which normal cells cannot survive. Another fascinating fact about biofilm is that cells are differentially expressed to form different layers within biofilm.
We continued to develop our project from two ideas based on the background. The first is based on biofilm’s differentiated expression. We hope to construct a three-layer stratified expression system within biofilm in response to oxygen concentration gradient. This could serve as a prototype for future construction simply by replacing the reporter gene with user’s target genes. The second idea stems from the biofilm’s strong resistance to bad growth conditions, such as when surrounded by high concentrations of heavy metal. We want to engineer and develop our biofilm into the second generation of biosensor. As a natural concentration gradient of heavy metal is formed along the depth of biofilm, with the same threshold for detection constructed in all the cells, the whole biofilm system would be able to detect different levels of the heavy metal concentration in its surrounding environment.

Gut Flora

We believe engineering gut bacteria is a promising field in the future, for bacteria are easy to be engineered compared with engineering human cell, and human gut is naturally inhabited by many different bacteria. We could construct a gut bacteria kit for either supplying nutrients such as vitamins or synthesizing and delivering drugs. We’re highly motivated to do this project, for it offers a good solution to alleviate the current famine and diseases brought by malnutrition in many developing countries around the world. The drug delivery, adapted to host’s circadium rhythm and physiological state, would be an ideal approach to cure some chronic diseases. However, we didn’t choose to further develop Gut Flora Kit as our team’s project this year, because we have limited knowledge and experience in gut flora and intestinal environment.

Alternative Splicing

Alternative splicing is a type of post-transcription mRNA modification observed in most multi-cellular organisms. It happens where there is more than one intron in a gene, meaning that different splicing site choices generate different mature mRNA thus produce different protein. The choice of the splicing site is controlled by a very complex system, yet we have some interesting and convincing understanding about it, and may it become a new perspective in synthetic biology.
In a multi-exon pre-mRNA, some exons are constitutively cut off or maintained, while some exons are sometimes skipped and sometimes kept. The latter is called an alternative splicing. The pattern can be controlled by many mechanisms involving a good many RNA secondary structure formations, protein-protein and protein-RNA interactions. Different splicing patterns always have relatively constant expression pattern in certain cell condition.
We are inspired by this interesting phenomenon and hope to design a new synthetic biology tool which can use compiled gene to produce many different kinds of proteins under different conditions.
We are inspired by a consistent mechanism of splicing pattern determination, which is called the mutually exclusive splicing. Every time only one out of several exon cassettes(altering exons) are presented. Latest discoveries revealed this is affected by certain pre-RNA secondary structure. If we change the sequence of the regulatory region, we may change the splicing pattern, and some proteins are expressed in a regulated and constant way.
One big problem about this idea is the chassis. Multi-cellular life-form is not very suitable for synthetic biology, and there is no such system in bacteria. So yeast becomes the only solution we can come up with. Very few alternative splicing is reported in yeast, yet it can normally carry out the pre-RNA processing function. Another is that changing the gene sequence to control the expression pattern is too difficult to apply.
Finally, we suspended this idea and tried to find other doable and potential projects.