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.
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.
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
Love it or hate it, E. coli is a “Jack of all trades”. Fifty years of research has made this small organism the best characterized living thing on the planet. And, this activity doesn’t look like it will let up anytime soon. With all the molecular biology tools available for E. coli, adding or removing genes can be successfully completed within a week (if you are in a hot streak). Manipulating its metabolism genetically can lead to production of a desired molecule or protein of up to 90% the total cellular output. In other words, you can turn E. coli towards ethical slavery.
With the increasing ease of synthetic biology, manipulating E. coli is becoming more sophisticated. Introducing entire metabolic pathways complete with gene regulators is now possible. One can now envision feeding E. coli plant biomass and it pooping out diesel fuel.
Thanks to the decreasing costs of sequencing genomic DNA, finding novel microorganisms that add to our understanding of metabolism in myriad environments is becoming common place. Not only are we learning about the diversity of life in extreme environments, like heat, cold, pressure, and altitude, but we are also learning what life on other planets may be like. With each additional genome added into ‘the cloud’, our synthetic biology toolbox gets a little bit bigger and our ability to manipulate tiny organisms to produce novel compounds is possible. Enter the “rushing fireball”.
Pyrococcus furiosus is an archeal species that thrives near deep-sea thermal vents where temperatures are between 90 and 100 degrees Celsius (or 194 to 212 degrees F). P. furiosus can grow at temperatures as low as 70 degrees C (158 deg F). To live in such conditions, this organism’s proteins must be tolerant to what we would consider harsh conditions. This organism’s ambient conditions makes wild-type proteins well-suited for industrial processes where temperatures are near boiling.
So far, P. furiosus has been utilized to produce 3-hydroxypropionic acid, a common industrial chemical used to make various products including acrylics. The kicker is that these cells were wired to make this chemical from atmospheric carbon dioxide. It is not crazy to think of what other useful products can be produced by P. furiosus with small modifications within the genome; products like ethanol or butanol as biofuels.