Solving the world’s problems with new biotechnology

The ability to isolate, create, synthesize, or artificially evolve living organisms towards desirable phenotypes may be increasingly important for solving many of the problems the world is facing. Such problems may include creating renewable energy using biowaste, finding biocontrol products that kill food-spoiling fungi “organically”, or assaying pathogens in the field using synthetic biological detection systems. With the arrival of synthetic biology, “it is possible to design and assemble chromosomes, genes and gene pathways, and even whole genomes”, according to the J. Craig Venter Institute. That is, if you know which genes or gene pathways you would need to put into the synthetic genome that would lead to the desired traits. So far, most published synthetic biology work involves bringing in transcription factors from a non-host source to set up an artificial network like circadian oscillators, showing that it can be done and it is interesting.

Through the process of evolution biological systems aptly self-engineer favorable traits in order to survive, but these changes require millions of years to manifest. However, there are quicker adaptations to environmental cues, such as developing antibiotic resistance, which can be achieved through a small number of mutations in hundreds or even dozens of generations. The question is how to harness this kind of adaptation for new strains that can be used as products with defined purposes? As a first requirement, you must have an assay for identifying the wanted mutants or method for augmenting their subpopulation, which is not necessarily easy and normally takes some clever designs to establish. Since evolutionary success in nature results from continuous “rounds” of gene mutagenesis, expression and selection, an evolution in the lab should ideally proceed with continuity. Previously, each round of mutation and selection takes a few days to complete. Recently, Esvelt et al. in David Liu’s lab at Harvard demonstrated one way of doing in vitro continuous evolution, by creating a lagoon of mixed E. coli and phages. By continuous dilution of the phage population through outflow, those phages that remain in the pool with properties that help them propagate in the host bacteria will have a better chance to regenerate and accumulate mutations towards the design of the assay [1].

Another aspect of natural evolution is that it occurs in a heterogeneous environment separated into niches of subpopulations with uneven stress levels. Although most evolutions with human intervention were conducted in a homologous population under the same stress and selection, a spatially complex environment may speed up evolution. This may not be easy to imagine, but if a mutant acquires some level of resistance to its environmental stress level and has a chance to move to join a population under higher stress, its relative fitness will likely increase. In addition, in a smaller population in the niche under higher stress, the mutant with marginally beneficial properties acquired under lower pressure can take over more quickly. This was demonstrated by Zhang et al. who showed that with a gradient of antibiotics applied to an array of microwells interconnected through tiny channels, new resistant strains can evolve in less than a day. Without the gradient, or separate the interconnected niches into discrete wells, no resistant populations could be obtained [2].

With more understandings like these and equipped with large scale gene synthesis, chromosome assembly, and deep sequencing technologies, we should see increasing numbers of human-made organisms serving special needs for food, health, energy, and the environment. Synthetic biology or artificial evolution won’t solve all the world’s problems, but if applied effectively and diligently, they can certainly help with many critical aspects as the technology “coevolves” with the environment.

[1] Kevin M. Esvelt, Jacob C. Carlson, & David R. Liu. “A system for the continuous directed evolution of biomolecules” Nature 499, 2011.
Qiucen Zhang, Guillaume Lambert, David Liao, Hyunsung Kim, Kristelle Robin, Chih-kuan Tung, Nader Pourmand, Robert H. Austin. “Acceleration of Emergence of Bacterial Antibiotic Resistance in Connected Microenvironments” Science 333, 2011.

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Tags: biocontrol, bioenergy, biofuel, biowaste, chromosome assembly, deep sequencing, food fungus, green energy, in vitro evolution, microenvironment, next generation sequencing, synthetic biology

Recap from the San Diego Entrepreneur Exchange March Event on Green Energy

With the recent concerns about the safety of nuclear power originated from the Japan earthquake and Tsunami, it should be beneficial for us to recap what we have learned at the latest SDEE conference two days before the natural disaster hit Japan.

Ron Pitt, CEO of EcoDog:
Solar energy is a great source of energy but it’s limited by the supply of silicon. Furthermore solar panels have a life of about 20 years, at which point they need to be replaced. It’s important that we take steps to alleviate our dependence on oil and deal with the current crisis, but it is also imperative that we employ forward thinking, and expand the time scale so our fix doesn’t last 20 years, or even 200 years but much longer.

Barry Toyonaga, CBO of Kent BioEnergy:
Algea is probably the most efficient way of removing waste material in waters and to entice nutrition to soil. Even the biomass after use has been shown for making bricks in a recent conference in Japan. It is important to use every aspect of our raw material, we must be so efficient to the point where no useless waste is generated by the end of our process.

Steve Mayfield, Director of the San Diego Center for Algae Biotechnology, UCSD:
The energy generated from petroleum-derived fuels as well as chemicals are used for high efficiency production of food. The emission of CO2 peaked by many magnitudes in recent centuries and coincided with human population explosion. The fast depletion of oil will soon reduce humans’ abilities to produce food at such high efficiency, and unavoidably will lead to famine and population reduction. The recent unrest in Africa is not a fight for democracy but a fight for food (which we can’t agree).

The green industry is young and needs supporting roles even after high rollers like Sapphire Energy, a company spun out by Mayfield and recently received major equity investment from Monsanto, take all the spotlight. There are engineering work to be done to process the oil produced by algae, to manage production and transportation, etc.

Sandy Madigan, CEO of Strategic Enzyme Applications:
Lignin is a naturally present macromolecule in wood and other plants, it is very carbon rich and one of the few natural sources aromatic compounds can be derived from. If broken down effectively lignin can serve as an alternative source of carbon compounds, with the current source being petroleum. Furthermore, as a source of aromatics, it has the potential to provide an exact fuel replacement, as opposed to most current research looking for fuel alternatives.

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Tags: biofuel, green energy, Japan earthquake, melt down, nuclear power plant, renewable energy, tsunami, US West coast