Life Science Technologies
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While the next-generation sequencing machines used by Diversigen and others remain hugely popular, another option since 2015
has been the MinION used by Rhodes and produced by Oxford
Nanopore Technologies in the United Kingdom. It feeds DNA strands
through nanopores in a membrane. At the same time, it runs a current through those pores. As adenines, thymines, cytosines, and
guanines pass through the pore, each changes the current in a
slightly different way, allowing the MinION to read the sequence.
The device, little bigger than a USB stick, can read multiple
strands at once through many pores, and collects lengthy reads,
unlike shotgun sequencing of short pieces, making the MinION par-
ticularly useful for assembling a full microbial genome.
The MinION was the perfect solution for molecular virologists at
the University of Leuven in Belgium, when veterinarians sent them
mystery samples from lesions growing on the faces of giraffes in
South African and Danish zoos. Piet Maes and his group prefer to
send more than just a few such samples to the traditional next-gen
sequencer they typically use—they would rather wait until they can
deliver 40–160 samples.
Eager to get the giraffe results, Bert Vanmechelen, a Ph.D. student in Maes’ laboratory, fired up the MinION instead. “With the
MinION we can do it at our own computers, prepare the sample on
day one, and get the results on day two,” he explains. In that short
amount of time, he was able to sequence the genome of a new kind
of papillomavirus, which the researchers named Giraffa Camelopardalis papillomavirus 1. There’s no cure for this strain of virus, so the
giraffes required surgery to remove the lesions—but it was useful to
know that the infection was nothing more severe, says Maes.
The MinION also has field capability; it was used to follow the
Ebola virus evolution during the recent African epidemic, and has
even been rocketed up to the International Space Station.
Rhodes and Vanmechelen each had a single microbe to
sequence, but for groups of organisms, it’s more complicated.
Microbiologists seem to be moving away from simply identifying
types of microorganisms from rRNA genes, toward more in-depth,
whole-genome sequencing, says Sheila Connelly, vice president for
Before researchers like those at Enterome can start crunching
data, however, they have a more basic problem—obtaining samples.
At the Arkansas Children’s Research Institute in Little Rock, clinical researcher John Slattery and colleagues study the causes and
physiology of autism spectrum disorder (ASD). Lately, they’ve been
focusing on the gut microbiome, which might be responsible for the
gastrointestinal complaints of many with ASD, as well as the mitochondrial dysfunction researchers have observed in them.
Slattery would like to conduct further studies on the gut microbiome of ASD patients, but there’s a catch. Stool donations are
difficult to acquire—donors must use an unwieldy container called
a “collection hat.” For both kids and parents, that’s a distasteful
prospect. Complicating matters, 80% of children with ASD have
constipation, diarrhea, or an alternating pattern of both.
That’s why Slattery is so keen on the BioCollector, developed by
The BioCollective in Centennial, Colorado. It hooks conveniently onto
the toilet lid and then closes up, “like a terrible present,” he says.
“You don’t ever have to see it.”
The BioCollective, founded in 2015, creates an unusual partnership between people willing to send in their stool samples and scientists who want to study them. Members purchase a BioCollector for
US$39.95; once they’ve filled it and mailed it in, their gut microbes
will be identified as accurately as possible by rRNA gene sequencing. They are also promised 10% of the profits from every aliquot of
their feces that The BioCollective sells to scientists.
Those researchers, in turn, get easy, efficient, and low-cost access to diverse stool samples. These come complete with donor
data, such as antibiotics they’ve taken or stresses they’ve endured.
The company even hopes to develop a standard “reference” sample—a sort of “poo stew” made of combined healthy samples, says
CEO and cofounder Martha Carlin.
Moreover, The BioCollective can provide samples from people
with a certain condition or on a specific diet. For example, Noah
Zimmerman, a biochemist at Agro BioSciences in Wauwatosa, Wis-
consin, is interested in how polyphenols—the colorful and beneficial
compounds in fruits and vegetables—affect the microbiome. To help
Zimmerman, The BioCollective recruited people willing to adopt a
Once researchers have their samples, they have a couple of options
for genomic analysis, and need not perform the work themselves if
they don’t want to. There are a number of contract research organiza-
tions willing to handle sequencing and analysis, such as CosmosID
of Rockville, Maryland; Diversigen of Houston, Texas; and Second
Genome Solutions in South San Francisco, California.
For purified organisms, one can simply sequence the genome or
the transcriptome to identify gene expression patterns. That alone
will yield plenty of insights, notes Nur Hasan, vice president and
head of R&D at CosmosID. The company can sequence a purified
culture from its clients, then perform bioinformatics analyses to
provide such information as where it fits in a phylogenetic tree of
microorganisms, what antibiotic-resistance genes it harbors, what
virulence factors it carries, and more.
For companies developing microorganisms for use in food or
medicines, knowing the full sequence of the microbe in question
is crucial, notes Jean-Philippe Laine, director of business
development at Diversigen. P H O
A device that collects
multiple lengthy reads,
the MinION is particularly
useful for assembling a
full microbial genome,
such as one from a novel