Precision Tinkering of Cells, Genes & Microbes: The Big Idea Finalists

Xconomy Boston — 

Biology research has gotten so precise these days that scientists barely bat an eye when they talk about their ability to study the genome of individual cells or swap out single “letters” in DNA. So it’s probably no surprise that ultra-precise ways of measuring and manipulating cells, molecules and microbes have found their way into biotech companies—and into the Big Idea category of the Xconomy Awards. Other finalists aim to tinker with microbes in new ways for human health and agriculture. But all are working on ideas that promise to change the way drugs are discovered, diseases are diagnosed and treated, or food is produced. Here are the 2018 Big Idea finalists. The winner will be announced at our gala on September 5.

See stories profiling the other finalists in the CEO, Startup, Digital Trailblazer, and Innovation at the Intersection categories, as well as the winner of the Lifetime Achievement award.

Day Zero Diagnostics – Rapid Test for Antibiotic Resistance
Determining the best antibiotic to use for a particular infection is still largely a trial-and-error exercise. Doctors can send a sample from a patient to a lab where technicians grow the bacteria in a dish, throw various drugs at them, and see which one works. But the process of growing the bacteria can take days, and for serious infections like sepsis, that can be too late for the patient.

Day Zero Diagnostics is working on a faster way of finding out which antibiotic will kill a certain bacterium from a patient—something that’s critical given that the growth of antibiotic resistance shows no signs of slowing down. The two-year-old startup is developing new laboratory techniques that allow researchers to tease out tiny amounts of bacteria from a sample—as little as one “colony forming unit” per milliliter (a low number in the world of microbiology)—without having to grow the microbe in the lab, says Jong Lee, Day Zero’s CEO. He co-founded the company with Miriam Huntley, the company’s chief technology officer.

The company then sequences the genome of the tiny amount of bacteria. Its goal is to then set its machine learning algorithm loose on the genomic data to identify not just the bacterium’s species, but also which antibiotic it’s susceptible to. Lee says his team has trained its algorithm to tease out genetic signatures linked to specific antibiotic vulnerabilities. He adds that the company is now working to automate this process, so that the technology can be used in hospital microbiology labs. The company hopes to start validation testing of its technology using real patient samples later this year.

Day Zero announced a $3.5 million seed round of funding last year and is working to raise its Series A round.

Ginkgo Bioworks – Synthetic Biology for Agriculture
Ginkgo has turned synthetic biology into a business, genetically engineering microbes to churn out industrial chemicals like flavors and fragrances on a large scale. But last year, it moved into agriculture, forming a $100 million joint venture with multinational giant, Bayer. Its goal is to develop microbes that take nitrogen from the air and turn it into a form that plants can use. The microbes would be applied to crops to reduce the need for nitrogen fertilizer.

The joint venture, called Joyn Bio, is tackling a major problem in agriculture. Plants rely on microbes to “fix” nitrogen for them, but most crop plants don’t have, or don’t have enough of these microbes, causing farmers to apply large amounts of nitrogen fertilizer that can pollute the environment. Nitrogen-fixing microbes as ag products aren’t new, but Ginkgo is bringing its synthetic biology technology and manufacturing capabilities to the table to engineer microbes that are more efficient at this process.

Joyn, headquartered within Ginkgo’s space in Boston, is also looking for other ways synthetic biology can be applied to agriculture, such as tackling crop diseases like soybean rust. It has another facility in West Sacramento, CA, where Bayer has greenhouses it will use to test plants treated with the new microbes. Ginkgo has said that greenhouse testing could begin within three years.

Human Cell Atlas – Mapping Cells of the Body
The Human Cell Atlas has embarked on an ambitious quest to genetically profile all the different types of cell in the body, by zooming in and studying single cells. An international consortium of more than 600 scientists—led by Aviv Regev of the Broad Institute and Sarah Teichmann of the Wellcome Sanger Institute in the UK—is doing this by sequencing tens of millions of individual human cells from healthy volunteers. The aim is to catalogue the thousands of cell types according to their gene activity patterns and even pinpoint their location within tissues and the body. The research could also show how the cells interact with each other.

Through this work, the researchers hope to discover new cell types, including ones that might be involved in disease. Cell Atlas leaders have said that comparing healthy cells with diseased ones could yield new disease mechanisms and hence better drugs, and diagnostic blood tests could become more informative.

Launched two years ago, the project released its first data earlier this year. A Broad team posted raw data of genetic profiles of half a million human immune cells. Researchers from the Wellcome and others released data from cells from a mouse tumor model and the human spleen. Making raw data openly available is a key tenet of the consortium.

Regev recently co-founded Cambridge, MA-based Celsius Therapeutics, which is using some of the same single-cell genomics technologies as the Human Cell Atlas to study cells from specific groups of patients and find new drug targets in autoimmune disease and cancer. The company launched with $65 million in series A financing this year.

Kaleido Biosciences – Drugging the Microbiome
Most human microbiome companies are trying to shift the balance of microbes living in the gut by delivering actual microbes. But Kaleido, a three-year old startup, is targeting the gut microbiome differently, by designing chemicals that gut microbes consume as nutrients. This, in turn, alters the metabolism of the microbes, changing the level of certain metabolites that the bacteria produce.

Research is increasingly showing how these metabolites affect key biological processes in a wide range of diseases. For example, the microbiome produces 40 to 70 percent of the … Next Page »

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