New Illustration: Yeastie Boys, a powerhouse for synthetic biology

Yeast image, science as art, microbe
An interpretation of the yeast Saccharomyces cerevisiae, a model for synthetic biology
When it comes to synthetic biology, two species of microorganisms should automatically come to mind; E. coli and the yeast Saccharomyces cerevisiae.  Both have been used extensively for proof of principle research. Thanks to these investigations, both are able to synthesize a drop-in biodiesel. 

More Yeastie Boys images available here.

 

Germs, for lack of a better word, are good. Germs are right. Germs work. Germs clarify, cut through, and capture, the essence of the evolutionary spirit.

To paraphrase a great movie classic, Wall Street. 

I want to change focus a bit, from bacteria benefiting mankind by cleaning up our messes and providing electricity, to another great benefit of bacteria; their pliability. It is very easy to manipulate the genetics of bacteria (see Biohacking). This owes to their genome structure and lack of miles of “junk” DNA. This means scientists can insert genes from one bacterium into a more well-known bacterium, like E. coli, to perform a novel function and, in a way, reverse millions of years of evolution. For example, in 2011, Jay Keasling and his team at the Joint BioEnergy Institute (JBEI) modified E. coli to degrade switchgrass biomass into sugars. Not only that, the E. coli fermented the sugars into gasoline, diesel, or jet fuel without enzyme additives. Think about it; E. coli, a bacterium that colonizes the digestive tracts of mammals, is able to breakdown plant material and directly convert it into fuel. That is amazing. I’m working on an illustration to depict this, so check back. 

 

Bacteria Chemotaxis Explained with Animated GIFs. Bacterial Behavior in Motion

bacteria, chemotaxis, random bias
With no attractant or repellant, bacteria have a “random bias”. This means they switch direction randomly.
bacteria, chemotaxis, attractant response
When bacteria are in an attractant gradient (colored orange), they switch direction less often when attractant concentration is higher.
bacteria, chemotaxis, repellant response
However, when a repellant is present (colored red), bacteria switch direction more often in high repellant concentrations.

 

 

How do bacteria make decisions? Part 2

bacterial, motility, chemotaxis
The path bacterial cells swim tracked using motion tracking software

Yesterday, we looked at one of the first factors (or protein families specifically) that guide bacteria in their decisions. Which direction to travel is not the only decision needed to be made by bacteria (more coming soon). I wrote about methyl-accepting chemotaxis proteins (MCPs) briefly (more visuals to come). These proteins interact directly or indirectly by sensing changes caused by chemical compounds from the bacterium’s environment. Today I will briefly write about the next step towards decision making in a bacterial cell in regards to direction of travel. MCPs by themselves would be useless if they did not interact with some other cellular machinery. Lucky for bacteria, the MCPs are only the first of many specialized proteins for regulating direction of travel. If a chemical binds to an MCP outside the cell, how does the inside of the cell get the message? When chemicals bind to an MCP or stop binding to it, it slightly changes the structure of the MCP. It is thought association or dissociation of chemicals to MCPs causes a rotation like a slight turn of a door knob. Depending on if the MCPs are rotated or not changes the activity of another enzyme that interacts with MCPs, a protein called CheA (pronounced, ‘key A’). When CheA is active, it converts two other proteins into an active form, CheB and CheY. Confused yet? When CheY is in its active form, it interacts with the base of the flagellum and causes the flagellum to switch direction of rotation and causes the bacterium to change the direction it is moving. The take home message for the mechanism is this: when the MCPs are not interacting with chemicals (nutrients), CheA and CheY are active, and the flagellum switches rotation to make the cell go in a different direction. Hopefully for the cell, the new direction it is traveling will have more nutrients that will interact with the MCPs and block more changes in direction by CheA/CheY activity.

You might ask, if chemical compounds are always bound to the MCPs, what if the cell begins going to passed the best environment and needs to turn around? Good question. That is where the other protein activated by CheA comes in, CheB. What makes this system unique is the ability to adapt to current conditions (nutrient chemical levels) so the cell can respond to new information. A set of protein enzymes act upon part of the MCPs that can cause a change in how rotated (think door knob again) the MCP is. If the MCP is always interacting with a nutrient, a protein called CheR changes the MCP structure and causes rotation back towards the non-interacting form of the MCP. When CheA is active, it can activate CheB which reverses the changes caused by CheR. Ultimately, the whole system remains sensitive to new information over a wide range of nutrient concentrations (a 1000-fold range).

This whole system and its parts and regulation took several years for me to understand. I’m sure I did not do it justice, but hopefully you can get a small glimpse into the truth about “simple” bacteria.

In Part 3, I will discuss other decisions that bacteria make besides which direction to go in search of the promised land of milk and honey, or in this case, carbon and nitrogen sources.

A Gram-negative bacterial flagellum
A Gram-negative bacterial flagellum (Photo credit: Wikipedia)

MyTH: A new weekly series about one bacterial species. First Post: Escherichia coli

This thought came to my head as I couldn’t sleep last night. My Tiny Highlight (MyTH) will be weekly and will showcase interesting or useful bacteria. For the first installment, I will focus on the gold standard of biology; Escherichia coli or E. coli. E. coli was discovered in 1885 by a German doctor in feces of healthy people. He called it Bacterium coli commune because it was found in the colon. The classification system of bacteria was much different before the ability to sequence DNA as novel bacteria were initially classified and named by their shape and motility. The name later changed to Bacillus coli before finally being reclassified and named Escherichia coli after the original discoverer. How would you like it if someone named a bacteria from feces after you?

E. coli receives a bad reputation thanks to pathogenic strains that force recalls of all kinds of food products. However, those strains are very uncommon as E. coli is one of the most abundant species found in the GI tract of mammals. Also, without this bacterium, many of the scientific discoveries of the past 50 years would not be possible including solving protein 3D structures, mass production of insulin, and understanding signal transduction; the process of a cell sensing surrounding signals or cues and responding to them in a way that is favorable for the cell. One reason E. coli was such a well suited model organism is the doubling time or time to divide one cell into two daughter cells. A doubling time of only 20 minutes means in less than 48 hours, the mass of E. coli cells would roughly be equal the the mass of Earth and have the combined volume equalling a 1 meter thick layer of bacteria covering the entire surface of Earth (including oceans). This is incredible and gives E. coli a major advantage over slower growing bacteria.

I want to discuss, briefly, a major influence of mine. Julius Adler was born in Germany and became a lover of Nature as a child. He was fascinated with butterflies. adler

His lifelong passion has been behavior of living things. Luckily, he spent most of his professional career studying chemotaxis in E. coli although he now studies fruit flies. Adler is known as the father of chemotaxis, or the movement of a cell in response to sensing chemical signals. His landmark early papers in the journal Nature about chemotaxis in E. coli in 1966 and his later paper on the chemoreceptors, the proteins that interact with the surrounding chemicals, in E. coli laid the foundation that maid the chemotaxis system of E. coli the best characterized signaling pathway in Biology. In regards to chemotaxis, however, E. coli is on the simplistic side of the scale. For example, E. coli has 5 chemoreceptors and 1 chemotaxis operon, or a stretch of genes that are transcribed into RNA together but lead to distinctly different proteins that usually interact with each other. Through the explosion of genome sequencing, scientists can scan newly sequenced bacteria genomes for chemotaxis genes. The average number of chemoreceptor genes is roughly 5 times more than E. coli (~25) and it is more common for bacteria to harbor multiple chemotaxis operons suggesting most bacteria have evolved to use chemotaxis for regulate more than the motility behavior in these cells.

Let’s think a minute about why E. coli is ‘stupid’ compared to other bacteria. By ‘stupid’ I mean, they have less capacity to integrate signals from their surroundings into a cell response. Why doesn’t E. coli have 25 chemoreceptors, for example? For the answer, we just need look at where this microbe is found. The GI tract of mammals is fairly constant meaning there is less need to scavenge for a new home or adjust to changes in temperature or nutrients. We as mammals have no problems eating meaning E. coli has no problem eating as well. How about the other sequenced bacteria? They predominantly live in more variable environments like soil or oceans where is would be to their advantage to be able to sense a lot of chemicals or nutrients in their surroundings. Therefore, through evolution, they have acquired new abilities to sense through duplicating genes and mutating DNA favorably. Changing only a few nucleotide bases (A,C,G,T) could mean acquiring the ability to physically interact with different environmental chemicals that could serve as an energy source. Nature is awesome and she knows how to keep us, as observers, guessing.

You may feel I am biased about chemotaxis ( I am). This was my dissertation work in another bacterium. Check back next week when I will highlight a little known (publicly) soil bacterium, Azospirillum brasilense. If you have any comments, questions, or suggestions PLEASE LET ME KNOW!

 

Recommended reading about Julius Adler.

Wanted: A Nation of Bill Nyes. Making science mainstream, fun, and relevant. Part 4. « Taking Science to the People

Wanted: A Nation of Bill Nyes. Making science mainstream, fun, and relevant. Part 4. « Taking Science to the People

In my humble opinion, keeping a child’s curiosity and imagination alive is a major step towards having real progress in attitudes and participation in STEM education. I personally wanted to be a doctor growing up. I was fascinated with how all cell types worked together. The checks and balances. As I grew older, in came the question of what specialty to go into as a medical professional. Knowing my interests, it seemed no ‘specialty’ was specialized enough. Then while working at a summer internship at the Oak Ridge National Laboratory, I went into an office with the Biochemical Pathways wall poster.
Metabolic_Pathways_for_plotter_landscape_quantized.png
I could not take my eyes off of this masterpiece. To me, this poster symbolized life at the smallest scale but yet so sophisticated and precise; not to mention the signal transduction pathways that mediate the pathways output at any given time. I had found my calling. This visualization of what I had been taught in biology classes at all levels and biochem classes in college came to fruition.
For others, I’m sure it is different and I’m sure it’s not for everyone. The goal, inspire as many as possible to explore their curiosity of how life works and how they could make it better. Now the question, how do we do it?