Archaea Gaining Traction as New Source of Biotechnology Discovery

Designed to Cure

Drawing of the h. walsbyi archaean. Image source: Wiki Commons

Researchers are always eager to find unexplored troves of biology that can be tapped for new biotechnology research. After the home-run of CRISPR’s discovery within archaeans, the entire domain of Archaea is being looked upon with eager eyes.1  Archaeans still aren’t comprehensively understood, but the properties that certain members of Archaea possess are appealing for future applications in biotechnology. In particular, archaeans can tolerate extreme environments, avoid detection by the human immune system during colonization of a human host and are known to be a part of the human gut microbiome.2 As every microbiologist knows, effective software management of bacterial data is critical to successful research. This is twice as important when dealing with large volumes of completely new data about poorly understood microorganisms.  

A Little Bit About Archaeans

Archaeans haven’t been characterized as a distinct kingdom for very long, and early understandings of their properties has changed substantially.3 Terminology to describe archaeans is still inconsistent, with some researchers calling them by the antiquated term “archaeobacteria.” The biggest difference between bacteria and archaeans is the makeup of their cell membranes. The cell membrane of archaeans is composed of ether-linked lipids rather than ester-linked lipids like in all other organisms, allowing archaeans to survive environments that others might not.

Future research will master the production of archaean cell membranes and repurpose them for use in therapeutics that will operate in harsh environments. Engineering cells that can flourish in harsh environments could have a broad range of applications ranging from environmental cleanup to vaccine delivery. The logical starting point of this future research will be in the human gut microbiome.     

Since CRISPR, the primary area of investigation into archaeans has been the extreme and anaerobic environment of the human gut microbiome. Methanogenic archaeans within the gut microbiome have been implicated in diseases like IBD and periodontopathy.4 The gut microbiome is a hot area right now, and the addition of additional archaean studies to the mix will make grant money even easier to come by. Fleshing out useful metabolic pathways within archaeans will probably be accompanied by a quick patent application.

Research into archaeans within the microbiome isn’t technically or informatically easy, however. Accessing the 16S rRNA sequences required to differentiate archaeans from other members of the gut microbiome is notoriously difficult, and the bandwidth of the data that is generated requires robust algorithmic processing.5 Additionally, researchers of the microbiome (and those who have shared a lab with them) will attest to the unique logistical and olfactory difficulties associated with processing fecal samples.

Picking the Archaea Out From the Microbiotic Crowd

Many of the issues working with archaea isolated from the gut microbiome are similar to those investigating bacteria in the same environment. In order to investigate individual species of archaean from a sample of the human gut microbiome, the following data must be collected and sifted:

  • Human donor metadata
  • Human donor gastrointestinal phenotype and other measured health data
  • Human donor intestinal epithelial genotype
  • Up to date bacterial and archaean taxonomy data from other research
  • Known bacterial 16S rRNA sequences that are explicitly not of interest
  • Other bacterial 16S rRNA sequences that are explicitly not of interest
  • Known archaean 16S rRNA sequences that are explicitly not of interest
  • Other archaean 16S rRNA sequences that may be of interest
  • Archaean 16S rRNA sequences to be specifically studied

The fundamental problem of studying archaea within the gut microbiome is overlapping data. The genes of newly characterized archaeans will substantially overlap with previously discovered archaeans as well as bacteria. Co-occurrence analysis is an essential tool which allows for comparison between genetic profiles within the microbiome, but is limited by the number of characterized profiles. Each person’s gut microbiota is unique, and co-occurrence analysis with known microbiota and new archaeans spirals into vast amounts of data extremely quickly.6 In order to even approach co-occurrence analysis, a robust data management platform is required.  

Making Archaea That Will Work for You

The complexity of archaeans within the gut microbiome extends well beyond merely locating and sequencing them, however. The organisms within the gut microbiota have interactions with the host’s body as well as each other. To make matters worse, actions of the microbiome’s host can cause massive changes to the composition and functioning of the gut flora’s populations via influence on the host’s behavior.7 Behavioral consistency among human hosts is unlikely, which may explain why certain archaean populations are detected within the same host intermittently.

The following host and colony relationships must be characterized in order to rigorously study archaea within the gut microbiome:

  • Host actions which affect the microbiome enough to disrupt its homeostatic equilibrium or return it there from a state of disruption or degradation
  • Normal homeostatic microbiome interactions with host body outside of the gut
  • Normal homeostatic microbiome interactions with host body in the gut
  • Normal homeostatic microbiome interactions with host immune system, if any
  • Normal homeostatic microbiome interactions within itself
  • Disrupted homeostasis microbiome interactions with the host body and immune system
  • Disrupted homeostasis microbiome interactions within itself
  • Microbiome interactions with host body and immune system while returning to normal homeostatic state after disruption
  • Microbiome interactions within itself while returning to normal homeostatic state after disruption
  • Microbiome contribution to the generation of the gut microenvironment under normal, disrupted, and stabilizing conditions
  • Host contributions to the generation of the gut microenvironment under normal, disrupted, and stabilizing conditions
  • Host actions or immune responses which directly affect the archaean population of interest specifically
  • Host actions or immune responses which indirectly affect the archaean population of interest by changing other populations within the microbiome

The casual mention of microbiome interactions within itself belies an additional can of worms which incurs an even greater data load. The gut microbiome, like larger biomes, is in a constant flux of dynamic equilibrium between the species that live there and the environment which they both create and are shaped by. Archaeans within the gut microbiome are no exception.

Future research that wishes to understand archaeans for the purposes of researching new biotechnologies will have to delve into the interactions between the species of the gut microbiome and their environment:  

  • Individual bacterial species’ contribution to the generation of the gut microenvironment
  • Bacterial colony interaction with other bacteria which contribute to the microenvironment or alter their relative population proportions
  • Bacterial interaction with archaeans which contribute to the microenvironment or alter their relative population proportions
  • Individual archaean species’ contribution to the generation of the gut microenvironment
  • Archaean colony interaction with other archaeans which contribute to the gut microenvironment
  • Archaean interaction with other archaeans which impacts  relative population proportion of the archaean species of interest
  • Target species interactions with itself via horizontal gene transfer or genetically mediated changes to the influencing of the microenvironment
  • Species of interest transcriptome under different microenvironment and host homeostasis conditions

Each of these interactions requires the management of large quantities of host and colony genetic and physiological data. Compromising and using an imperfect software suite to handle data generated by research into archaeans will result in lost insights. There is only one informatics platform which can accommodate the management, tracking, and analysis of the different types of data required for research into archaeans.

Designed to Cure is the data management, collaboration, and experiment planning software that can handle the unique challenge of archaean microbiota research. Using Designed to Cure, analyzing vast data sets containing different levels of organization is a snap. Contact us today to find out how we can help you get on the fast track to developing the next generation’s archaean-derived therapeutics.

  1. “CRISPR/Cas, the immune system of bacteria and archaea.” January 2010, https://www.ncbi.nlm.nih.gov/pubmed/20056882
  2. “Archaea and Their Potential Role in Human Disease.” February 2003, http://iai.asm.org/content/71/2/591.full
  3.  “Biotechnology of the Archaea.” 1992, http://www.sciencedirect.com/science/article/pii/016777999290257V
  4. “Archaea as emerging, fastidious members of the human microbiota.” August 2012, http://onlinelibrary.wiley.com/doi/10.1111/j.1469-0691.2012.03904.x/full
  5. Methanomassiliicoccus luminyensis gen. nov., sp. nov., a methanogenic archaeon isolated from human faeces.” August 2012, https://www.ncbi.nlm.nih.gov/pubmed/22859731
  6.  “Pan-genome of the dominant human gut-associated archaeon, Methanobrevibacter smithii, studied in twins.” March 2011, https://www.ncbi.nlm.nih.gov/pubmed/21317366
  7. “Exploring Host-Microbiome Interactions using an in Silico Model of Biomimetic Robots and Engineered Living Cells.” July 2015, http://www.nature.com/articles/srep11988