Outreach

An interview with Dr Rosie Young, an expert on the development of genetic tools for the expression of foreign proteins in the microalgal chloroplast

The challenges and how CUO has helped
CUO has helped Dr Young’s group to design transgenes that are theoretically optimised for expression in the chloroplast of Chlamydomonas reinhardtii. She hopes this will increase the level of protein production so that microalgae can compete successfully with other expression platforms (eg. E. coli and mammalian cell culture) in the future. There is no direct evidence to show that optimisation using CUO is beneficial yet, but the results so far are encouraging.

Opinions on the current development of open source software
Dr Young stressed that freeware programs are very useful for molecular biologists. She uses programs on the web for tasks like:
• DNA sequence translation
• Reverse complementation
• Protein structure prediction
• Sequence comparison
The programs are either provided by bioinformatics institutes or by individual labs. She has mentioned that she does not have the need to adapt any programs for her own use but open source software would easily enable that if necessary.

Possible downsides of the open source characteristics of CUO
From a research lab point of view, she does not think there is a downside, as long as the program is rigorously tested and a paper is published about it as soon as possible. This will enable other groups to use the program as they wish. However, she did point out that the best thing to do would be to keep the program available to download via the lab's research pages only while the validation is ongoing and allow members of the lab to maintain and improve it. Once the lab has the scientific evidence that optimisation using CUO is beneficial, then the whole scientific community can benefit.

Workshops

A workshop was organized on the 24th October 2012, at UCL Foster Court 233 to introduce CUO to the public. The workshop elicited attention from students of various background- ranging from undergraduates to postgraduates, and from several disciplines.

We were proud to have Henry returning to the workshop to provide support for the team. He is one of the first users of CUO and is an expert in codon optimization. Most participants were unaware of how codon usage affects translation efficiency. This means codon optimization could play an important role in improving protein expression. Many interesting ideas were exchanged throughout the workshop and one hour of an introductory lecture has proven to be too short for us to guide our new users through the software.

Several participants find that the workshop was inspiring and said that they will definitely incorporate this software in their research. However, they hope that there will another session to provide a more thorough demonstration on how to use the software. Some were also curious of how the algorithm in the software works. Based on these feedbacks, we will strive to tailor our workshop towards the needs of the new users in the future. Watch out for more workshops to come!

In the meantime, we have asked one of the participants of the workshop several questions relating to the potential of CUO: We have interviewed Izzat Ismail, a final year Biotechnology student at UCL. In his final year project, he aims to produce an X-ray structure of LCAT protein which plays crucial roles in cholesterol homeostasis.

The challenges and how CUO will help

The main challenge that Izzat encounters is the protein expression itself. Previous studies done had failed to express and hence, produce protein that perfectly folded as in its native state. He believes that codon optimization could be one of the solutions to this problem. He envisioned that CUO will help with optimization of protein expression in different expression systems to help him obtain pure crystallized LCAT. He is excited to share the idea of the software with his supervisor!

Possible downsides of the open source characteristics of CUO

He mentioned that he is impressed with the development and advancement but suggested that more funding/grant should be provided for sustain such development. He is also happy with the direction of the development of these open source software. This is because developers have not solely focused on producing more advanced or robust software with lots of added characteristics, but have also paid attention to making them more user friendly.

Tutorials

Open Source Philosophy

Safety

• Synthetic gene technology has developed to such an extent that now it has become easier to use and implement. Now with software available to help in design, coupled with cheapening synthetic gene services, the technological barrier is becoming even lower for normal people to engineer genes. This can be good but also bad because it will be considerably easier to engineer nasty biological product or even bioweapons. Bioterrorism will be easy to do either purposely or accidentally by not properly trained individuals playing the genes as some kind of hobby.
• Proposed Solution: track the ordering customer's identity. Pattern check the ordered synthetic sequence and prevent unlicensed customers from ordering potentially dangerous genes.

• There is a misconception about codon optimization that changing the coding sequence of a wild type gene and transforming it may cause unintented products. The truth is actually the other way round. If a wild type gene is to be transformed into a foreign host, the wild type gene does already have the risk of producing unintended effect in the host. By doing rational optimization and sequence design, the unitended effects can be identified and eliminated instead.