Tag Archives: Paul S. Weiss

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.

Nanotechnology and the US mega science project: BAM (Brain Activity Map) and more

The Brain Activity Map (BAM) project received budgetary approval as of this morning, Apr. 2, 2013 (I first mentioned BAM in my Mar. 4, 2013 posting when approval seemed imminent). From the news item, Obama Announces Huge Brain-Mapping Project, written by Stephanie Pappas for Yahoo News (Note: Links have been removed),

 President Barack Obama announced a new research initiative this morning (April 2) to map the human brain, a project that will launch with $100 million in funding in 2014.

The Brain Activity Map (BAM) project, as it is called, has been in the planning stages for some time. In the June 2012 issue of the journal Neuron, six scientists outlined broad proposals for developing non-invasive sensors and methods to experiment on single cells in neural networks. This February, President Obama made a vague reference to the project in his State of the Union address, mentioning that it could “unlock the answers to Alzheimer’s.”

In March, the project’s visionaries outlined their final goals in the journal Science. They call for an extended effort, lasting several years, to develop tools for monitoring up to a million neurons at a time. The end goal is to understand how brain networks function.

“It could enable neuroscience to really get to the nitty-gritty of brain circuits, which is the piece that’s been missing from the puzzle,” Rafael Yuste, the co-director of the Kavli Institute for Brain Circuits at Columbia University, who is part of the group spearheading the project, told LiveScience in March. “The reason it’s been missing is because we haven’t had the techniques, the tools.” [Inside the Brain: A Journey Through Time]

Not all neuroscientists support the project, however, with some arguing that it lacks clear goals and may cannibalize funds for other brain research.

….

I believe the $100M mentioned for 2014 would one installment in a series totaling up to $1B or more. In any event, it seems like a timely moment to comment on the communications campaign that has been waged on behalf of the BAM. It reminds me a little of the campaign for graphene, which was waged in the build up to the decision as to which two projects (in a field of six semi-finalists, then narrowed to a field of four finalists) should receive a FET (European Union’s Future and Emerging Technology) 1 billion euro research prize each. It seemed to me even a year or so before the decision that graphene’s win was a foregone conclusion but the organizers left nothing to chance and were relentless in their pursuit of attention and media coverage in the buildup to the final decision.

The most recent salvo in the BAM campaign was an attempt to link it with nanotechnology. A shrewd move given that the US has spent well over $1B since the US National Nanotechnology Initiative (NNI) was first approved in 2000. Linking the two projects means the NNI can lend a little authority to the new project (subtext: we’ve supported a mega-project before and that was successful) while the new project BAM can imbue the ageing NNI with some excitement.

Here’s more about nanotechnology and BAM from a Mar. 27, 2013 Spotlight article by Michael Berger on Nanowerk,

A comprehensive understanding of the brain remains an elusive, distant frontier. To arrive at a general theory of brain function would be an historic event, comparable to inferring quantum theory from huge sets of complex spectra and inferring evolutionary theory from vast biological field work. You might have heard about the proposed Brain Activity Map – a project that, like the Human Genome Project, will tap the hive mind of experts to make headway in the understanding of the field. Engineers and nanotechnologists will be needed to help build ever smaller devices for measuring the activity of individual neurons and, later, to control how those neurons function. Computer scientists will be called upon to develop methods for storing and analyzing the vast quantities of imaging and physiological data, and for creating virtual models for studying brain function. Neuroscientists will provide critical biological expertise to guide the research and interpret the results.

Berger goes on to highlight some of the ways nanotechnology-enabled devices could contribute to the effort. He draws heavily on a study published Mar. 20, 2013 online in ACS (American Chemical Society)Nano. Shockingly, the article is open access. Given that this is the first time I’ve come across an open access article in any of the American Chemical Society’s journals, I suspect that there was payment of some kind involved to make this information freely available. (The practice of allowing researchers to pay more in order to guarantee open access to their research in journals that also have articles behind paywalls seems to be in the process of becoming more common.)

Here’s a citation and a link to the article about nanotechnology and BAM,

Nanotools for Neuroscience and Brain Activity Mapping by A. Paul Alivisatos, Anne M. Andrews, Edward S. Boyden, Miyoung Chun, George M. Church, Karl Deisseroth, John P. Donoghue, Scott E. Fraser, Jennifer Lippincott-Schwartz, Loren L. Looger, Sotiris Masmanidis, Paul L. McEuen, Arto V. Nurmikko, Hongkun Park, Darcy S. Peterka, Clay Reid, Michael L. Roukes, Axel Scherer, Mark Schnitzer, Terrence J. Sejnowski, Kenneth L. Shepard, Doris Tsao, Gina Turrigiano, Paul S. Weiss, Chris Xu, Rafael Yuste, and Xiaowei Zhuang. ACS Nano, 2013, 7 (3), pp 1850–1866 DOI: 10.1021/nn4012847 Publication Date (Web): March 20, 2013
Copyright © 2013 American Chemical Society

As these things go, it’s a readable article for people without a neuroscience education provided they don’t mind feeling a little confused from time to time. From Nanotools for Neuroscience and Brain Activity Mapping (Note: Footnotes and links removed),

The Brain Activity Mapping (BAM) Project (…) has three goals in terms of building tools for neuroscience capable of (…) measuring the activity of large sets of neurons in complex brain circuits, (…) computationally analyzing and modeling these brain circuits, and (…) testing these models by manipulating the activities of chosen sets of neurons in these brain circuits.

As described below, many different approaches can, and likely will, be taken to achieve these goals as neural circuits of increasing size and complexity are studied and probed.

The BAM project will focus both on dynamic voltage activity and on chemical neurotransmission. With an estimated 85 billion neurons, 100 trillion synapses, and 100 chemical neurotransmitters in the human brain,(…) this is a daunting task. Thus, the BAM project will start with model organisms, neural circuits (vide infra), and small subsets of specific neural circuits in humans.

Among the approaches that show promise for the required dynamic, parallel measurements are optical and electro-optical methods that can be used to sense neural cell activity such as Ca2+,(7) voltage,(…) and (already some) neurotransmitters;(…) electrophysiological approaches that sense voltages and some electrochemically active neurotransmitters;(…) next-generation photonics-based probes with multifunctional capabilities;(18) synthetic biology approaches for recording histories of function;(…) and nanoelectronic measurements of voltage and local brain chemistry.(…) We anticipate that tools developed will also be applied to glia and more broadly to nanoscale and microscale monitoring of metabolic processes.

Entirely new tools will ultimately be required both to study neurons and neural circuits with minimal perturbation and to study the human brain. These tools might include “smart”, active nanoscale devices embedded within the brain that report on neural circuit activity wirelessly and/or entirely new modalities of remote sensing of neural circuit dynamics from outside the body. Remarkable advances in nanoscience and nanotechnology thus have key roles to play in transduction, reporting, power, and communications.

One of the ultimate goals of the BAM project is that the knowledge acquired and tools developed will prove useful in the intervention and treatment of a wide variety of diseases of the brain, including depression, epilepsy, Parkinson’s, schizophrenia, and others. We note that tens of thousands of patients have already been treated with invasive (i.e., through the skull) treatments. [emphases mine] While we hope to reduce the need for such measures, greatly improved and more robust interfaces to the brain would impact effectiveness and longevity where such treatments remain necessary.

Perhaps not so coincidentally, there was this Mar. 29, 2013 news item on Nanowerk,

Some human cells forget to empty their trash bins, and when the garbage piles up, it can lead to Parkinson’s disease and other genetic and age-related disorders. Scientists don’t yet understand why this happens, and Rice University engineering researcher Laura Segatori is hoping to change that, thanks to a prestigious five-year CAREER Award from the National Science Foundation (NSF).

Segatori, Rice’s T.N. Law Assistant Professor of Chemical and Biomolecular Engineering and assistant professor of bioengineering and of biochemistry and cell biology, will use her CAREER grant to create a toolkit for probing the workings of the cellular processes that lead to accumulation of waste material and development of diseases, such as Parkinson’s and lysosomal storage disorders. Each tool in the kit will be a nanoparticle — a speck of matter about the size of a virus — with a specific shape, size and charge.  [emphases mine] By tailoring each of these properties, Segatori’s team will create a series of specialized probes that can undercover the workings of a cellular process called autophagy.

“Eventually, once we understand how to design a nanoparticle to activate autophagy, we will use it as a tool to learn more about the autophagic process itself because there are still many question marks in biology regarding how this pathway works,” Segatori said. “It’s not completely clear how it is regulated. It seems that excessive autophagy may activate cell death, but it’s not yet clear. In short, we are looking for more than therapeutic applications. We are also hoping to use these nanoparticles as tools to study the basic science of autophagy.”

There is no direct reference to BAM but there are some intriguing correspondences.

Finally, there is no mention of nanotechnology in this radio broadcast/podcast and transcript but it does provide more information about BAM (for many folks this was first time they’d heard about the project) and the hopes and concerns this project raises while linking it to the Human Genome Project. From the Mar. 31, 2013 posting of a transcript and radio (Kera News; a National Public Radio station) podcast titled, Somewhere Over the Rainbow: The Journey to Map the Human Brain,

During the State of the Union, President Obama said the nation is about to embark on an ambitious project: to examine the human brain and create a road map to the trillions of connections that make it work.

“Every dollar we invested to map the human genome returned $140 to our economy — every dollar,” the president said. “Today, our scientists are mapping the human brain to unlock the answers to Alzheimer’s.”

Details of the project have slowly been leaking out: $3 billion, 10 years of research and hundreds of scientists. The National Institutes of Health is calling it the Brain Activity Map.

Obama isn’t the first to tout the benefits of a huge government science project. But can these projects really deliver? And what is mapping the human brain really going to get us?

Whether one wants to call it a public relations campaign or a marketing campaign is irrelevant. Science does not take place in an environment where data and projects are considered dispassionately. Enormous amounts of money are spent to sway public opinion and policymakers’ decisions.

ETA Ap. 3, 2013: Here are more stories about BAM and the announcement:

BRAIN Initiative Launched to Unlock Mysteries of Human Mind

Obama’s BRAIN Only 1/13 The Size Of Europe’s

BRAIN Initiative Builds on Efforts of Leading Neuroscientists and Nanotechnologists