The Microbiome: Can We Please Consider the Human Body an Ecosystem Now?

It has long been thought the type and amount of microbes using the human body as a home shape the way we live and behave. The microbiome as it is known is shown to have a greater and greater impact in our daily lives.

A new study published in Nature (paywall) provides evidence demonstrating the artificial sweeteners we all love and consume to control weight leads to increased blood glucose levels. How can something used to replace sugar in consumables raise the amount of sugar in the blood?

Like many other answers regarding human health, look no further than the microbiome. Consuming artificial sweeteners alters the composition of the intestinal microbes leading to a growing glucose intolerance. The researchers linked artificial sweetener use to altering metabolic pathways within the microbiome that leads to increased susceptibility to metabolic disease.

To verify their findings, researchers gave antibiotics to the mice used as models thus reversing the effects of artificial sweeteners. Results were also verified by using fecal transplantation in the mice to reverse glucose intolerance.

The Human Microbiome: Our Ecosystem

We already knew the microbes outnumbered our human cells 10 to 1 and that the microgenome outnumbered our human genome 100 to 1. The evidence is growing suggesting our normal flora govern more of our lives than we naively assumed for decades. We are not individuals but individual incubators for the microbial overlords that we could not live without. Just like other ecosystems, changing our lifestyles have a complicated effect on system as a whole. Small alterations to the microbiome can have major impacts and be the difference between health and disease.

Future posts will hopefully provide evidence demonstrating how we are shaped into individual ecosystems. Thank you, microbiome.

 

Storytelling in Science: The Cell as Your Favorite Restaurant Part II

Recap: The restaurant is the bacterial cell, the employees are the proteins/enzymes that serve the patrons which are the compounds/metabolites.

Who are the bosses that determine which, and how many, employees are needed for each type of patron?

The restaurant managers have a very important job to perform. They have to make sure the right number of employees are available to help their respective patron. If the balance between employees and patrons is not well maintained, it could cause disaster for the restaurant itself. In a past post, I tried to describe how bacteria made decisions. One of the predominant ways was the use of two-component systems. For this story, think of the restaurant managers as actually two people who need to work well together. One identifies its respective patrons and the other makes changes to the number of employees for those patrons. It is this balancing act that helps the entire restaurant to work smoothly.

A successful restaurant will open up new locations. The same can be said for bacteria. If conditions are right, the cell will divide into two cells. As with a cell, restaurants have to make sure certain activities are undertaken to ensure the new restaurant will be exactly like the successful one it is copying. The success of this restaurant is based upon the ability to keep the employees happy (by having patrons to serve and not sitting around bored) and keeping the patrons coming in. To duplicate this success, the new restaurant should have a building exactly like the current one so the patrons will easily continue to enter and leave. The new restaurant will also need the exact employee list for the managers to call upon when needed. The employee list is the genome of the cell that encodes the proteins needed for survival. That would make the copy machine that duplicates the employee list the DNA replication machinery. This special restaurant building is state of the art. It can expand until it is roughly double its original size then place a dividing wall down the middle of the large building until the building becomes actually two buildings. Now the restaurant can serve twice the number of patrons with the same efficiency as before. Each new building has the same employee list and rough the same number of employees to start off with. Then the managers start their work identifying the patrons in the restaurant to make sure the employees are there to serve them.

The two buildings shake hands and go their merry way…ready to serve.

In Part III, I will talk about the intercom system that allows major changes to happen to the kind of employees needed for economic downturns.

“Groundbreaking” ‘Duon’ Paper Only Continues Research From Prior Studies

There is a lot of chatter on the internets about the press release from the University of Washington about a paper published in the journal Science this week. One claim within the press release is that findings in the present study uncover a ‘hidden’ code within human DNA that scientists had no prior knowledge of. As many have written, this assumption is completely false and grossly exagerated.

After reading the paper (paywall), I can say the study does add a wealth of new information to an already known phenomenon. I recommend reading the article if one is in the molecular biology or human genetics fields. However, the press release about this study should be retracted for the amount of misleading claims raised within it.

In fact, the authors write in the final paragraph,

Our results indicate that simultaneous encoding of amino acid and regulatory information within exons is a major functional feature of complex genomes. The information architecture of the received genetic code is optimized for superimposition of additional information (3435), and this intrinsic flexibility has been extensively exploited by natural selection. Although TF binding within exons may serve multiple functional roles, our analyses above is agnostic to these roles, which may be complex (36).

Pay close attention to the parenthetical numbers within the quote. These indicate the statement is referencing a prior publication. 34 is reference to a paper from 2007 in Genome Research entitled, “The genetic code is nearly optimal for allowing additional information within protein-coding sequences.” and can be found here. 35 is a paper from 2010 also in Genome Research; “Overlapping codes within protein-coding sequences.” found here. And 36 is from Nature Genetics earlier this year entitled, “DNase I–hypersensitive exons colocalize with promoters and distal regulatory elements” found here.

A question for UW Today,

If these authors uncovered an unknown, hidden code within DNA, how could they reference earlier studies that essentially elaborated upon these same ‘secrets’?

I’ll be waiting for an answer…

Nanobiopsy: the beauty in the very small is a big deal

The ability to study the living without destroying it has been the goal of many scientists for decades. A new article in ACS Nano has paved the road towards noninvasive cellular-level examination. The only true way to study cellular dynamics is to study a single cell over time (temporally). The reason for this is the heterogeneous nature of any cell culture because no two cells are identical spatially and temporally. Each individual cell has its own set of experiences that has generated its current molecular inventory, ie. RNA molecules, metabolites, proteins, sugars, lipids, etc. Studying a community of cells gives rise to noise that makes finding significant differences incredibly difficult.

In the article entitled Compartmental Genomics in Living Cells Revealed by Single-Cell Nanobiopsy, the authors used a kind of microscopy called scanning ion conductance microscopy, or SICM, that allows for continuous sampling of a single cell over time. The authors used a nanopipette as part of the SICM and combined this with sensitive sequencing techniques resulting in a high resolution look at what genes are being expressed over time into RNA molecules. Furthermore, this technique was used to study the genomic information of individual mitochondria within a single cell without also studying the nuclear material. In other words, this new technique has resulted in the ability to not only study cellular dynamics, but go beyond that and study subcellular dynamics.

This breakthrough will have impacts across many fields from cancer biology to improving climate models.

Paolo Actis, Michelle M. Maalouf, Hyunsung John Kim, Akshar Lohith, Boaz Vilozny, R. Adam Seger, & Nader Pourmand (2013). Compartmental Genomics in Living Cells Revealed by Single-Cell Nanobiopsy ACS Nano DOI: 10.1021/nn405097u

The Tree of (the Study of) Life

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First full genome sequencing for autism: Promise for future diagnosis, prevention and treatment

First full genome sequencing for autism: Promise for future diagnosis, prevention and treatment.

Illustration: Synthetic Biology; Turning bacteria poop into a hot commodity

bacteria art, E. coli art, bioenergy, biomass, biodiesel
Illustration showing the concept of E. coli engineered to digest plant cell wall material (green) and produce fatty acids (white) that can be used as diesel as a waste product. The fatty acids shown are actual 3D structures of linoleic acid.