Tag Archives: Rob Knight

Nano and a Unified Microbiome Initiative (UMI)

A Jan. 6, 2015 news item on Nanowerk features a proposal by US scientists for a Unified Microbiome Initiative (UMI),

In October [2015], an interdisciplinary group of scientists proposed forming a Unified Microbiome Initiative (UMI) to explore the world of microorganisms that are central to life on Earth and yet largely remain a mystery.

An article in the journal ACS Nano (“Tools for the Microbiome: Nano and Beyond”) describes the tools scientists will need to understand how microbes interact with each other and with us.

A Jan. 6, 2016 American Chemical Society (ACS) news release, which originated the news item, expands on the theme,

Microbes live just about everywhere: in the oceans, in the soil, in the atmosphere, in forests and in and on our bodies. Research has demonstrated that their influence ranges widely and profoundly, from affecting human health to the climate. But scientists don’t have the necessary tools to characterize communities of microbes, called microbiomes, and how they function. Rob Knight, Jeff F. Miller, Paul S. Weiss and colleagues detail what these technological needs are.

The researchers are seeking the development of advanced tools in bioinformatics, high-resolution imaging, and the sequencing of microbial macromolecules and metabolites. They say that such technology would enable scientists to gain a deeper understanding of microbiomes. Armed with new knowledge, they could then tackle related medical and other challenges with greater agility than what is possible today.

Here’s a link to and a citation for the paper,

Tools for the Microbiome: Nano and Beyond by Julie S. Biteen, Paul C. Blainey, Zoe G. Cardon, Miyoung Chun, George M. Church, Pieter C. Dorrestein, Scott E. Fraser, Jack A. Gilbert, Janet K. Jansson, Rob Knight, Jeff F. Miller, Aydogan Ozcan, Kimberly A. Prather, Stephen R. Quake, Edward G. Ruby, Pamela A. Silver, Sharif Taha, Ger van den Engh, Paul S. Weiss, Gerard C. L. Wong, Aaron T. Wright, and Thomas D. Young. ACS Nano, Article ASAP DOI: 10.1021/acsnano.5b07826 Publication Date (Web): December 22, 2015

Copyright © 2015 American Chemical Society

This is an open access paper.

I sped through very quickly and found a couple of references to ‘nano’,

Ocean Microbiomes and Nanobiomes

Life in the oceans is supported by a community of extremely small organisms that can be called a “nanobiome.” These nanoplankton particles, many of which measure less than 0.001× the volume of a white blood cell, harvest solar and chemical energy and channel essential elements into the food chain. A deep network of larger life forms (humans included) depends on these tiny microbes for its energy and chemical building blocks.

The importance of the oceanic nanobiome has only recently begun to be fully appreciated. Two dominant forms, Synechococcus and Prochlorococcus, were not discovered until the 1980s and 1990s.(32-34) Prochloroccus has now been demonstrated to be so abundant that it may account for as much as 10% of the world’s living organic carbon. The organism divides on a diel cycle while maintaining constant numbers, suggesting that about 5% of the world’s biomass flows through this species on a daily basis.(35-37)

Metagenomic studies show that many other less abundant life forms must exist but elude direct observation because they can neither be isolated nor grown in culture.

The small sizes of these organisms (and their genomes) indicate that they are highly specialized and optimized. Metagenome data indicate a large metabolic heterogeneity within the nanobiome. Rather than combining all life functions into a single organism, the nanobiome works as a network of specialists that can only exist as a community, therein explaining their resistance to being cultured. The detailed composition of the network is the result of interactions between the organisms themselves and the local physical and chemical environment. There is thus far little insight into how these networks are formed and how they maintain steady-state conditions in the turbulent natural ocean environment.

Rather than combining all life functions into a single organism, the nanobiome works as a network of specialists that can only exist as a community

The serendipitous discovery of Prochlorococcus happened by applying flow cytometry (developed as a medical technique for counting blood cells) to seawater.(34) With these medical instruments, the faint signals from nanoplankton can only be seen with great difficulty against noisy backgrounds. Currently, a small team is adapting flow cytometric technology to improve the capabilities for analyzing individual nanoplankton particles. The latest generation of flow cytometers enables researchers to count and to make quantitative observations of most of the small life forms (including some viruses) that comprise the nanobiome. To our knowledge, there are only two well-equipped mobile flow cytometry laboratories that are regularly taken to sea for real-time observations of the nanobiome. The laboratories include equipment for (meta)genome analysis and equipment to correlate the observations with the local physical parameters and (nutrient) chemistry in the ocean. Ultimately, integration of these measurements will be essential for understanding the complexity of the oceanic microbiome.

The ocean is tremendously undersampled. Ship time is costly and limited. Ultimately, inexpensive, automated, mobile biome observatories will require methods that integrate microbiome and nanobiome measurements, with (meta-) genomics analyses, with local geophysical and geochemical parameters.(38-42) To appreciate how the individual components of the ocean biome are related and work together, a more complete picture must be established.

The marine environment consists of stratified zones, each with a unique, characteristic biome.(43) The sunlit waters near the surface are mixed by wind action. Deeper waters may be mixed only occasionally by passing storms. The dark deepest layers are stabilized by temperature/salinity density gradients. Organic material from the photosynthetically active surface descends into the deep zone, where it decomposes into nutrients that are mixed with compounds that are released by volcanic and seismic action. These nutrients diffuse upward to replenish the depleted surface waters. The biome is stratified accordingly, sometimes with sudden transitions on small scales. Photo-autotrophs dominate near the surface. Chemo-heterotrophs populate the deep. The makeup of the microbial assemblages is dictated by the local nutrient and oxygen concentrations. The spatiotemporal interplay of these systems is highly relevant to such issues as the carbon budget of the planet but remains little understood.

And then, there was this,

Nanoscience and Nanotechnology Opportunities

The great advantage of nanoscience and nanotechnology in studying microbiomes is that the nanoscale is the scale of function in biology. It is this convergence of scales at which we can “see” and at which we can fabricate that heralds the contributions that can be made by developing new nanoscale analysis tools.(159-168) Microbiomes operate from the nanoscale up to much larger scales, even kilometers, so crossing these scales will pose significant challenges to the field, in terms of measurement, stimulation/response, informatics, and ultimately understanding.

Some progress has been made in creating model systems(143-145, 169-173) that can be used to develop tools and methods. In these cases, the tools can be brought to bear on more complex and real systems. Just as nanoscience began with the ability to image atoms and progressed to the ability to manipulate structures both directly and through guided interactions,(162, 163, 174-176) it has now become possible to control structure, materials, and chemical functionality from the submolecular to the centimeter scales simultaneously. Whereas substrates and surface functionalization have often been tailored to be resistant to bioadhesion, deliberate placement of chemical patterns can also be used for the growth and patterning of systems, such as biofilms, to be put into contact with nanoscale probes.(177-180) Such methods in combination with the tools of other fields (vide infra) will provide the means to probe and to understand microbiomes.

Key tools for the microbiome will need to be miniaturized and made parallel. These developments will leverage decades of work in nanotechnology in the areas of nanofabrication,(181) imaging systems,(182, 183) lab-on-a-chip systems,(184) control of biological interfaces,(185) and more. Commercialized and commoditized tools, such as smart phone cameras, can also be adapted for use (vide infra). By guiding the development and parallelization of these tools, increasingly complex microbiomes will be opened for study.(167)

Imaging and sensing, in general, have been enjoying a Renaissance over the past decades, and there are various powerful measurement techniques that are currently available, making the Microbiome Initiative timely and exciting from the broad perspective of advanced analysis techniques. Recent advances in various -omics technologies, electron microscopy, optical microscopy/nanoscopy and spectroscopy, cytometry, mass spectroscopy, atomic force microscopy, nuclear imaging, and other techniques, create unique opportunities for researchers to investigate a wide range of questions related to microbiome interactions, function, and diversity. We anticipate that some of these advanced imaging, spectroscopy, and sensing techniques, coupled with big data analytics, will be used to create multimodal and integrated smart systems that can shed light onto some of the most important needs in microbiome research, including (1) analyzing microbial interactions specifically and sensitively at the relevant spatial and temporal scales; (2) determining and analyzing the diversity covered by the microbial genome, transcriptome, proteome, and metabolome; (3) managing and manipulating microbiomes to probe their function, evaluating the impact of interventions and ultimately harnessing their activities; and (4) helping us identify and track microbial dark matter (referring to 99% of micro-organisms that cannot be cultured).

In this broad quest for creating next-generation imaging and sensing instrumentation to address the needs and challenges of microbiome-related research activities comprehensively, there are important issues that need to be considered, as discussed below.

The piece is extensive and quite interesting, if you have the time.

3D cartographies and histories of the skin

Here’s some ‘skin news’, from a March 30, 2015 University of California at San Diego news release (also on EurekAlert),

Researchers at the University of California, San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences used information collected from hundreds of skin swabs to produce three-dimensional maps of molecular and microbial variations across the body. These maps provide a baseline for future studies of the interplay between the molecules that make up our skin, the microbes that live on us, our personal hygiene routines and other environmental factors. …

The researchers have produced a video illustrating a ‘skin map’,

Credit for 3D mapping and video: Theodore Alexandrov;
Credit for data collection: Christopher Rath

The news release goes on to explain what makes this work special,

“This is the first study of its kind to characterize the surface distribution of skin molecules and pair that data with microbial diversity,” said senior author Pieter Dorrestein, PhD, professor of pharmacology in the UC San Diego Skaggs School of Pharmacy. “Previous studies were limited to select areas of the skin, rather than the whole body, and examined skin chemistry and microbial populations separately.”

To sample human skin nearly in its entirety, Dorrestein and team swabbed 400 different body sites of two healthy adult volunteers, one male and one female, who had not bathed, shampooed or moisturized for three days. They used a technique called mass spectrometry to determine the molecular and chemical composition of the samples. They also sequenced microbial DNA in the samples to identify the bacterial species present and map their locations across the body. The team then used MATLAB software to construct 3D models that illustrated the data for each sampling spot.

Despite the three-day moratorium on personal hygiene products, the most abundant molecular features in the skin swabs still came from hygiene and beauty products, such as sunscreen. According to the researchers, this finding suggests that 3D skin maps may be able to detect both current and past behaviors and environmental exposures. The study also demonstrates that human skin is not just made up of molecules derived from human or bacterial cells. Rather, the external environment, such as plastics found in clothing, diet, hygiene and beauty products, also contribute to the skin’s chemical composition. The maps now allow these factors to be taken into account and correlated with local microbial communities.

“This is a starting point for future investigations into the many factors that help us maintain, or alter, the human skin ecosystem — things like personal hygiene and beauty practices — and how those variations influence our health and susceptibility to disease,” Dorrestein said.

It was somewhat startling to realize clothing becomes part of my skin’s chemical composition rather than protecting it or, where allergies are concerned, affecting it. In effect, this map seems as much history as geography.

Here’s a link to and a citation for the paper,

Molecular cartography of the human skin surface in 3D by Amina Bouslimani, Carla Porto, Christopher M. Rath, Mingxun Wang, Yurong Guo, Antonio Gonzalez, Donna Berg-Lyon, Gail Ackermann, Gitte Julie Moeller Christensen, Teruaki Nakatsuji, Lingjuan Zhang, Andrew W. Borkowski, Michael J. Meehan, Kathleen Dorrestein, Richard L. Gallo, Nuno Bandeira, Rob Knight, Theodore Alexandrov, and Pieter C. Dorrestein. PNAS March 30, 2015 doi: 10.1073/pnas.1424409112 Published online before print March 30, 2015

This is an open access paper.

Brains, guts, health, and consciouness at TED 2014′s Session 5: Us

While most of the speakers I’m mentioning are the ‘science’ speakers in this session, they are more precisely ‘medical science’ speakers which takes me further than usual out of my comfort zone. That said, Nancy Kanwisher, brain researcher, opened the session (from her TED biography),

Using cutting-edge fMRI technology as her lens, Nancy Kanwisher zooms in on the brain regions responsible for some surprisingly specific elements of cognition.

Does the brain use specialized processors to solve complex problems, or does it rely instead on more general-purpose systems?

This question has been at the crux of brain research for centuries. MIT [Massachusetts Institute of Technology] researcher Nancy Kanwisher seeks to answer this question by discovering a “parts list” for the human mind and brain. “Understanding the nature of the human mind,” she says, “is arguably the greatest intellectual quest of all time.”

As many of us now know courtesy of researchers like Kanwisher, the brain has both general purpose regions and specialized regions for perception and complex processing but Kanwisher’s presentation was as much about the process of discovery as it was about the discoveries she and her colleagues have made. She talked about her personal experiences with functional magnetic resonance imaging (fMRI) as she tested (many times) her own brain first and then spent years looking at grayscale images as she decoded what she was observing and tested over and over and over again.

Next came the ‘gut guy’, or as microbial ecologist Rob Knight’s TED biography describes him,

Rob Knight explores the unseen microbial world that exists literally right under our noses — and everywhere else on (and in) our bodies.

Using scatological research methods that might repel the squeamish, microbial researcher Rob Knight uncovers the secret ecosystem (or “microbiome”) of microbes that inhabit our bodies — and the bodies of every creature on earth. In the process, he’s discovered a complex internal ecology that affects everything from weight loss to our susceptibility to disease. As he said to Nature in 2012, “What motivates me, from a pragmatic standpoint, is how understanding the microbial world might help us improve human and environmental health.”

Knight made the case that our microbes are what give us our individuality by noting that 99.99% of our DNA is the same from one person to the next but out microbial communities vary greatly person to person and the community in your mouth varies greatly from the community on your skin. He and his colleagues are using the information to consider new types of medical interventions. For example, research has shown that giving children antibiotics before the age of six months affects their future health.

Interestingly, we carry about 3 lbs. of microbes individually and Knight and his colleagues are still gathering information about those lbs. He mentioned the American Gut project (and solicited future volunteers from the live audience by mentioning he had just happened to bring 100 kits which were available at his table outside). This project is for US participant only.

Stephen Friend, oncologist and open science advocate was featured next. From his TED biography,

Inspired by open-source software models, Sage Bionetworks co-founder Stephen Friend builds tools that facilitate research sharing on a massive and revolutionary scale.

While working for Merck, Stephen Friend became frustrated by the slow pace at which big pharma created new treatments for desperate patients. Studying shared models like Wikipedia, Friend realized that the complexities of disease could only be understood — and combated — with collaboration and transparency, not by isolated scientists working in secret with proprietary data

Friend has a great name for someone who advocates for transparency and openness. He opened with stories about his work and how he came to be inspired to look for health rather than disease. He noted that for the most part, medical research is focused on the question of what went wrong with a patient rather than asking if healthy people have some sort of natural immunity or protection from cancer, Alzheimer’s, etc. Perhaps by examining health people we can find ways to more effectively intervene.

He provided two examples of research that examined natural immunity such as research in San Francisco (California) into why a small but significant percentage of people with HIV never developed AIDS; his other example was regarding research into lipid levels and why some people with high levels never develop heart disease.

I’m a little foggy about this point but I think he made a request for information about these medical phenomena and people from around the world shared their research with him in an open and transparent fashion.

This next bit was clear to me, he and his colleagues are moving to another stage with their research initiative which they have named the Resilience Project; Unexpected Heroes. He too solicited volunteers from the audience. I haven’t been able to locate a website for the project but there maybe some on the Sage Bionetworks website, the organization Friend co-founded. Good luck!

Finally, I wasn’t expecting to write about David Chalmers so my notes aren’t very good. A philosopher, here’s an excerpt from Chalmers’ TED biography,

In his work, David Chalmers explores the “hard problem of consciousness” — the idea that science can’t ever explain our subjective experience.

David Chalmers is a philosopher at the Australian National University and New York University. He works in philosophy of mind and in related areas of philosophy and cognitive science. While he’s especially known for his theories on consciousness, he’s also interested (and has extensively published) in all sorts of other issues in the foundations of cognitive science, the philosophy of language, metaphysics and epistemology.

Chalmers provided an interesting bookend to a session started with a brain researcher (Nancy Kanwisher) who breaks the brain down into various processing regions (vastly oversimplified but the easiest way to summarize her work in this context). Chalmers reviewed the ‘science of consciousness’ and noted that current work in science tends to be reductionist, i.e., examining parts of things such as brains and that same reductionism has been brought to the question of consciousness.

Rather than trying to prove consciousness, Chalmers proposes that we consider it a fundamental in the same way that we consider time, space, and mass to be fundamental. He noted that there’s precedence for additions and gave the example of James Clerk Maxwell and his proposal to consider electricity and magnetism as fundamental.

Chalmers next suggestion is a little more outré and based on some thinking (sorry I didn’t catch the theorist’s name) that suggests everything, including photons, has a type of consciousness (but not intelligence).