As synthetic biology evolves there is a need to create larger and more complicated genetic systems. An appropriate system for designing lengthy, multi-protein plasmids and chromosomes requires an appropriate language and design platform. Despite using biological components, the language of computer programming has often been used to create synthetic genetic systems. As synthetic biology expands, a consensus language and development program becomes vital to allow the design of complex plasmids and even whole chromosomes.
Molecula Maxima is a high level programming language for designing and constructing genetic systems.
Produced by Mr. Eliad Moshe it allows researchers to design, debug, compile and optimise long stretches of DNA. Coming from a background in robotics, Eliad was initially excited by the idea of writing code to implement into biological systems. He developed the SyntheticTM programming language and the CytostudioTM integrated development language using tools from electronic engineering protocols. Eliad aims to transform the synthetic biology ecosystem to the scale of the semiconductors industry by democratizing the creation of drugs and GMOs to software developers and electronic engineers.
Visual drag and drop sequence design tools are simple and easy to use, and allow plasmid design from a limited set of sequences. In contrast, a specially designed programming software permits non-parallel scaling of DNA sequences and the use of accumulated knowledge. Sequences can be inserted into CytostudioTM manually, or copied from standard databases such as the Protein Data Bank and the iGEM BioBrick registry. Embedded web views within CytostudioTM allow these databases to be searched while carrying out DNA design. Entries can be viewed and edited as either DNA nucleotides or protein amino acids, and proteins can be visualised as solid molecules. The completed DNA can be viewed in either linear or circular annotated visual forms.
Based in Israel, Mr. Moshe began work on his synthetic programming language 5 years ago, launching the public beta in the autumn of 2015. In the last three months he has been advertising and promoting the product on facebook and social media. The software currently has over 180 users while the facebook page has more than 31.5 thousand likes.
“If we can design genetic circuits that are made from 1-3 plasmids, why stop there?” Eliad explains. “We can scale not only in massive parallelism but also with the complexity of very large scale integrated genetic circuits. In order to be able to design such systems, we must increase the level of abstraction and level of modularity and the best way to do that is by using a high-level bio-programming language.”
Once the sequence has been designed, it can be sent off for synthesis, and it is here that the real benefit of the increasingly lower prices of DNA synthesis becomes obvious. Molecula Maxima allows the construction of large chromosome-length pieces of DNA, which would be time consuming if not impossible to construct from component parts using conventional PCR gene splicing techniques. As the price of DNA synthesis continues to fall, researchers are constrained only by what they can imagine, rather than what they can afford to construct.
Designing a programming language for biological systems further opens up the sphere of synthetic biology to include computer programmers, allowing them to design modular biological systems as well as improving on the tools for DNA design and genetic machine development. With the increased modularity afforded by a biological programming language, a programmer could theoretically design and express their sequence within the biological system, without requiring a deep biological knowledge of DNA function or cell processes.
Although the programming language has been designed using engineering principles, Mr. Moshe believes that it is also intuitive for biologists and science researchers. The programming language has been especially popular for students involved in iGEM; the International Genetically Engineered Machine Competition that encourages students worldwide to use synthetic biology to create biological machines. The iGEM students are a mix of science and engineering undergraduates, who have used Molecula Maxima to design their biological machines, creating a length of DNA that can be sent off for synthesis.
As well as borrowing engineering principles for design, Eliad admires the open source and community based nature of program development. Projects developed using the Synthetic programming language can be shared as GitHub repositories, and CytostudioTM can be modified and extended with MiniApp plugins. Eliad has also set up SynBioForums for researchers to discuss and troubleshoot projects and hopes to encourage a strong community of bio-programmers to develop a broad database of accumulated knowledge.
As the Molecula Maxima software develops, he wants to develop combinatorial design modules to allow variations on DNA sequences to be designed and tested. He is also excited about the use of robotic cloud laboratories to allow scientists and programmers from all over the world to easily collaborate on projects and share new designs. “In the near future the synthetic biology ecosystem will evolve to the scale of the semiconductor industry.” He says, “Software developers and electronics engineers will manufacture high level genetically modified organisms and open source and free software drugs will dominate.”
While Molecula Maxima is still in bootstrapping phase, Eliad is already in talks with investors in both the USA and Israel. He is also in discussions with synthetic biology and DNA synthesis companies. He’s hoping to get to the stage where DNA can be designed and tested in a coding program, before being sent off for synthesis, with bacteria containing the final designed genome delivered directly to the door.
“The rise of bio-software.” Mr. Moshe finishes, “That is what I am here for.”