Synlogic – Synthetic Biology

You know the world is truly advanced when someone has invented a synthetic cell. And this happened five years ago. Enter the field of synthetic biology, defined as the use of molecular biology tools and techniques to construct genetic systems that produce a desired behavior.

With the decreasing price of DNA sequencing and synthesis, the ease of genetic engineering (CRISPR, molecular cloning), and the increase in computational capacity, we have reached a stage where creating an engineered cell, and making it do what you want is a possibility. Rooted from the discovery in 1961 by Jacob and Monad that bacteria have regulatory systems and circuits that control its interaction with its environment, the wide-spread use of ‘omics’ technology that followed allowed us to understand these circuits in detail. The subsequent rise in molecular engineering prowess – molecular cloning, recombinant technologies, gene editing, inducible promoters, light-sensitive promoters – has equipped man with the ability to engineer synthetic signalling pathways in the cell.

As understanding grew on how simple organisms such as bacteria, viruses and yeast sensed the environment and regulated their circuitry to respond to changes, scientists slowly found ways to produce sometimes entirely artificial circuits into these organisms, hijacking their systems to help man conquer even greater heights. Bacteria and viruses have been engineered to invade cancer cells, disperse biofilms, produce biofuel and synthesize drugs.

The main obstacles faced were designing parts of the circuit to talk to each other effectively, and making sure they work as designed in their specific context/environment. This was initially challenging but is getting easier with the ease of gene assembly, where whole genes can be synthesized by assembling short oligos together, allowing to build any circuit component independently. This is how Craig Venter created the first synthetic cell, assembling chemically-synthesized oligos into DNA chunks that were recombined in yeast to create an entire synthetic genome that was transplanted into a recipient bacterial cell that took on characteristics defined by the synthetic genome.

An up and coming biotech dealing in synthetic biology is Synlogic, founded by James Collins (Boston University) and his previous post-doc, Timothy Lu (MIT) in 2014. Their work focuses on developing therapeutic microbes which we ingest – that are engineered to interact with the gut microbiome to fight infection and chronic disease. The biotech has already accumulated $35 million in funding from investors which include the Bill and Melinda Gates Foundation, New Enterprise Associates and Atlas Venture. What’s more they recently snagged ex-Pfizer Senior VP and Head of Biotherapeutics R&D, JC Gutiérrez-Ramos as their CEO. Chief Scientific Officer Paul Miller is also a big pharma bigshot, serving as VP in Astrazeneca and before that in Pfizer. Alison Silva heads operations, previously also working for a biotech that dealt with engineered microbes. Though still in the early stages, the company has already presented in vivo efficacy data in its two lead programs targeting the orphan genetic metabolic conditions Urea Cycle Disorder (UCD) and Phenylketonuria (PKU). The details are not public but these synthetic microbes presumably detect changes in the gut microbiome and may even kill toxic cells.

Synthetic biology marries biology and engineering and scientist with mad skills in engineering genomes, building cellular circuits and understanding cellular systems would likely be in demand in years to come. So think big and stay friendly with bacteria.

Sources:

D. Ewen Cameron, Caleb J. Bashor & James J. Collins “A brief history of Synthetic Biology” Nature Reviews Microbiology 12,381–390 (2014) doi:10.1038/nrmicro3239

Why its great to be a Scientist today

As much as it has been said that we are producing far too many PhD graduates than we need, the current era of scientific progress I believe demands the production of far more good scientists to achieve the dream of a truly advanced techy world. Due to the lack of internet at the new apartment, we have been re-watching  Star Wars (yes true geeks we are). Perhaps the thing that made Star Wars so successful (and it honestly was not the acting) was how creatively imaginative George Lucas was at describing a world so futuristic, spacey and technological advanced at a time in history, (1977 to be exact) when such technology was so far from becoming reality.

In Munich, the Deutsche Museum houses an incredible amount of gadgets and equipment devised from the early ages till today ranging from ships, mining equipment, textile weaving machines, musical instruments, microscopes, computers, weighing instruments, radios, and much much more. The capacity for the human mind to imagine, invent and create is what separates us from the rest of the animal kingdom. We have done this for years and we will keep on doing it, because somehow man is never satisfied with the current state of affairs.

It is no different for the field of biological science, health and medicine. So you know, despite what they say, it is a great time to be a scientist. And why is now a great time? Just look around you. People are becoming more and more interconnected with the aid of mobile technology and the Internet. The ability to find, generate, store and disseminate information is easier than ever. The typical scientist can now read the latest research papers with the click of a mouse or even better, find and talk to an expert in the field. Running experiments have become much faster; consumables and reagents are delivered within the week, DNA sequencing results within 2 days. Work can be carried out on different continents with results shared instantly via email or web meetings. This is a time when ideas are so easily bounced around, which tends to generate even more ideas.

Perhaps for this reason, many big executives are leaving big pharma to start or join smaller biotech companies. Astrazeneca R&D Chief, Briggs Morrison, recently announced a sudden exit and will become CEO of a small privately-held pharmaceutical. Also this year, Jose-Carlos Gutierrez-Ramos, left his senior R&D role at Pfizer to become CEO of Synlogic, a company dealing with synthetic biology. Big pharmas used to be the only ones with enough money to develop drugs but with the growing interest in healthcare by investors, it is not difficult to find money to fund your very own pharma. In fact, sometimes it is becoming a little too easy. Smaller firms have the flexibility to pursue riskier ideas which big pharma cannot afford to do, and with the technology available today, it is the age where one can do truly amazing stuff.

The next few blog posts will cover some companies that are on the cutting edge of science in arenas such as genomic testing, gene therapy, health monitoring, data processing, and synthetic biology. So the question is, what key question are you working on? And are you fully utilizing the technologies of today in your research?