I was home today with the TV on. It was Ingenious Minds day on the Science Channel. A majority of the people showcased on the shows hadAutistic Spectrum Disorder, or ASD. After watching/listening to several episodes, something occurred to me as I was making dinner, who is to say we are the ones with an abnormal brain? Historically speaking, it would be very unlikely for the majority of the population to be abnormal.
But what if this was looked at from a different perspective? The growing prevalence of diagnosed autistic children could be observed as a rapid evolution of the human. Let’s say Mother Nature’s evolution experiment with humans. I have written about autism elsewhere (here) and how much of this disorder is a huge question mark to researchers. Progress is being made with university PR departments and other ‘media’ proclaiming it is all just a intestinal flora imbalance and is curable. Evidence supports a link between gut bacteria and several disorders, but it is immature to call it case closed.
I am left looking at this as naivete on our part. The autistic are the abnormal ones because we don’t understand their physiology. I just hope our descendents don’t look back at us ashamed of our folly.
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 field of stem cell research promises to deliver truly amazing medical breakthroughs in the coming decades. However, the fundamental research needed must first provide the proof-of-principle necessary for private industry to take note. That is happening according to a recent article published in the journal Blood. Researchers at Brigham and Women’s Hospital, Harvard‘s Stem Cell Institute, in collaboration with MIT and Mass General have successfully reprogrammed a type of connective tissue stem cell line, known as mesenchymal stem cells, to produce specific surface proteins and the anti-inflammatory molecule interleukin-10.
To accomplish this, researchers injected a modified form of messenger RNA, the blueprint for protein synthesis in cells. The modified stem cells were injected into mice. Once in the mouse bloodstream, the stem cells successfully targeted sites of inflammation and reduced swelling.
This approach is promising because it targets the site in need of therapeutics and can deliver the needed drug at a level high enough to provide results. This approach is attracting attention from large pharmaceutical companies because of the capability to target the disease site itself.
Oren Levy, Weian Zhao, Luke J. Mortensen, Sarah LeBlanc, Kyle Tsang, Moyu Fu, Joseph A. Phillips, Vinay Sagar, Priya Anandakumaran, Jessica Ngai, Cheryl H. Cui, Peter Eimon, Matthew Angel, Charles P. Lin, Mehmet Fatih Yanik, & Jeffrey M. Karp (2013). mRNA-engineered mesenchymal stem cells for targeted delivery of interleukin-10 to sites of inflammation Blood DOI: 10.1182/blood-2013-04-495119
We’ve been told for years that our body is composed of cells, human cells. We’ve also heard about the ‘good’ bacteria that inhabit our bodies and help us digest different types of food and can even provide us essential vitamins and nutrients. Most of this occurs in the small intestine where our food starts to become our poop. Pardon the pun, but what we’ve been told is grossly underestimated. First, they outnumber our cells…by a lot (10 to 1). That doesn’t include the overwhelming majority of genetic material in or on our bodies that is not ours (see infographic here).
More and more evidence is being presented showing the intimate relationship between man and his flora. First, these little guys provide more than just vitamins including some B vitamins and K. They also are able to absorb essential minerals, like calcium and iron, from our food for us to use later. They also provide a physical barrier to defend against infection from pathogens that may enter your digestive tract.
Recent research has shown a connection between gut bacteria and childhood eczema (here).
Another study indicates small molecules secreted by bacteria can prevent inflammatory bowel (here).
How about gut bacteria affecting the onset of rheumatoid arthritis (RA) in susceptible individuals (here).
One study found by eating probiotic yogurt, women had lower occurrence of depression (here).
These are just a few, picked examples establishing a relationship between bacteria, or the types of bacteria, in our guts and our health. What about examples?
Autism and gut bacteria
Research now suggests a link between autism spectrum disorder (ASD) and environmental factors. These may include a number of factors, but what about gut bacteria?
A recent article in PLoS ONE shows a significant decrease in GI bacterial diversity among autistic subjects compared to normal subjects. Some common bacterial genera were missing in autistic subjects, especially Prevotella. The missing bacteria were common carbohydrate-degrading species or fermenters. This, and other, evidence could explain the common GI irritability in autistic children. There is also some reports of changes in diet (gluten-free, caseine-free) lessening the effects of autistic symptoms.
It is still early, and much more needs to be studied. However, you shouldn’t think of yourself as a single entity. You and your bugs are a package deal.
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.
I can’t think of a better post to serve as my 300th. After a month and a half of teaching myself Autodesk Maya, I present my best animation yet, although it must’ve been by accident. I have two versions (two different file formats). But first, some background.
Many bacteria have developed strategies to grow and thrive within environments absent of oxygen. Instead of using oxygen to “breathe”, bacteria use alternative molecules (alternative electron acceptors) to dump the waste product from respiration (the electron). These molecules can range from bacterium to bacterium. Some of the most common alternative electron acceptors include nitrate, nitrite, and iron. Interestingly, these are some of the most prevalent land pollutants and our knowledge of the types of bacteria that can thrive under these conditions continues to grow. One of the most interesting observations, in my opinion, is the process of extracellular electron transfer, or EET. During EET, the bacteria with this property have devised a method to transfer their waste to their environment without having to actually import potentially dangerous compounds into the cell. Through a elaborate network of specialized proteins able to taxi electrons called cytochromes, bacteria like Geobacter and Shewanella are able to thrive within what we would consider extreme environments.
I’m only uploading one file due to file size, but if anyone is interested in the image sequence in .png to create their own animation with a background image, please feel free to let me know. So, here it is: Enjoy!
The marvels of single celled organisms is that they are able to integrate all kinds of stimuli and make one grand decision that affects how they proceed. Bacteria do in one cell what we as humans do with billions. However, do bacteria contain the ability to think as a group or community?
The answer is absolutely. It is called quorum sensing. The pioneer for this research is Bonnie Bassler from Princeton University. Listening to her tell her story of the curiosity she felt when observing how and why a certain group of bacteria emitted light, or bio-luminescence is great. (Watch here). Through her investigation with a insignificant bacterium, Vibrio harveyi, she opened up a whole new field of microbiology.
Many bacteria synthesize signaling molecules that serve as messages to other bacteria saying, “I am here”. Since bacteria don’t have senses that we are familiar with like sight and hearing, these signaling molecules tell other bacteria who is around. When there aren’t a lot of bacteria sending out the signal, no big decisions are made. However, when enough bacteria are around to tell all other village members the approximate population, all village members act together to make a committed decision. In the case of V. harveyi it is the production of a light emitting molecule, but for other bacterial species it may be activation of pathogenicity. From the perspective of the bacterium, you don’t want to decide alone to make a big commitment like invading another organism. By taking a bacterial census through quorum sensing, these bacteria make a educated decision only when their population is high enough to make an impact. For some species, this critical number may be less than ten. However, in some cases, the population needs to be in the millions.
I think bacteria can teach us a very important lesson via quorum sensing: don’t go it alone. It takes a village.