microbiology – TylerJFord.com

April 8, 2019April 8, 2019

Delving into SciComm by Tyler’s Instagram stories: Biosensors, Komodo dragons, lab meat, and more!

Stories from the SciComm by Tyler Instagram account

I often come across interesting biology facts. I spam these facts in polite conversation, but I’ve also decided to share them in a more productive way on Instagram. On the SciComm By Tyler instagram account, I’ll post detailed drawings coupled to nuggets of biological intrigue. Some of these will come from blog posts. Through the stories feature, I’ll share more bite-sized biological morsels. I’ll couple the stories with goofy doodles (sometimes I’ll recycle these from my gallery :P). At the end of each week, I plan on delving into the stories in a little more detail through a blog post.

Below, I expand on my first week of stories. Enjoy!

Please follow me on Instagram if you like what you see :D.

Biosensors are biological machines that detect objects and events

I wrote a bit about biosensors in an older blog post. As a refresher, biosensors are biological machines that detect specific objects and events. They have many research uses. They can detect chemicals, they can detect organisms, and some can even count how many times cells divide.

I first became enamored with biosensors during my PhD work. For part of my work, I tried to get bacteria to turn sugar into gasoline. To see if my bacteria were accomplishing this goal, I designed a biosensor. This biosensor made the bacteria turn red if they produced gasoline-like chemicals. Indeed, the more gasoline-like chemicals they produced, the more red they’d become. Unfortunately, my biosensor wasn’t particularly sensitive so I abandoned it (such is the nature of many experimental research projects!).

Others have created more useful sensors. The doodle above illustrates a biosensor that detects DNA. Such biosensors bind to specific DNA sequences and glow. They help scientists understand how DNA sequences interact with other things in cells. Using many different biosensors, scientists learn how cells function. Scientists can then use their knowledge to create therapeutics or even design cells that do cool things like attack cancer cells!

Komodo dragons use venom to kill prey

I think Komodo dragons are super cool. Even if they don’t breathe fire, they’re still basically dragons. Long ago, I was told that Komodo dragons don’t directly kill their prey. Supposedly, they instead transferred bacteria to their pray through biting. The resulting infections then killed their prey over time. Recently, I learned that RESEARCHERS DO NOT BELIEVE THIS ANYMORE. Indeed, when I was at the San Francisco Zoo a few days ago, I read that Komodo dragon bites inject venom into their prey. This venom kills prey through a mixture of physiological effects. For instance, the venom can lower blood pressure and prevent clotting. It’s not fire, but it’s pretty brutal!

Some frogs survive being frozen

Okay, I’m a molecular and cell biologist at heart, but I love me a good animal fact! I picked this one up while watching one of the many BBC nature documentaries on Netflix. I don’t have much more information than what’s in the image. I just think it’s really cool! Hopefully, I’ll dive into this in a dedicated post at some point.

Some bacteria inject DNA into plants

Doodle of an agrobacterium injecting DNA into a plant

Bacteria do soooooo much more than make us sick. There are many bacteria that do good things. We’ve even figured out how to turn some dangerous bacteria into useful tools. For example, there are bacteria that use teeny tiny needles to inject their DNA into plant cells. These bacteria naturally cause plant diseases. However, scientists have figured out how to use these bacteria to deliver useful DNA sequences to plants. They can even use these bacteria to make crops resistant to pests! Learn a little more about plant biotech in this post.

Complex meats are hard to make in the lab!

Many companies are working to grow meat and meat-like products in the lab. They hope to produce these “meats” more sustainably than livestock. They are having a lot of success growing meats like chicken nuggets or ground beef. However, it will be some time before we have more complicated meats like steaks or pork chops. The complex structures of these meats are difficult to create in the lab.

That’s all for this week. Please follow me on Instagram to check out my stories in real time. Cheers!

March 28, 2019March 28, 2019

From the BiLOLogy archives: E. coli fatty acid synthesis

In this post from the BiLOLogy archives, I discuss why I did my PhD work on E. coli fatty acid synthesis. This post was originally published back in August 2012 – the start of my 3rd year of graduate school. Enjoy!

Comic used to explain fatty acid synthesis

Why work on fatty acid synthesis? I can explain the reasoning by showing you the structure of a fatty acid (Figure 1):

Figure 1: Fatty acid (octanoate) structure

The corners connecting the black sticks in this fatty acid are carbons. The sticks themselves are bonds. All carbon atoms in any chemical compound need to be connected to other atoms by 4 bonds. NO MORE, NO LESS. The fatty acid can be broken into two regions: the fatty acid head (the part with all the O’s which are oxygens) and the tail, which consists of only carbons and hydrogens. The hydrogens are not drawn, but, if they were, the picture would look like this instead:

Figure 2: Fatty acid (octanoate) structure with all hydrogens (H’s) and carbons (C’s) labeled

Octanoate structure with all atoms labeled

Clearly, this figure is much less appealing, letters scattered all over the place and all, but we can see that all the carbon atoms have the appropriate number of bonds. The hydrogens simply aren’t drawn in the first figure.

What’s important is that all of these carbon-hydrogen bonds are full of potential energy. In fact, if we compare octane, a component of gasoline, to the fatty acid, we see that the fatty acid’s tail is nearly identical (figure 3). Indeed, through a variety of mechanisms, humans and bacteria can convert fatty acids into compounds, like octane, that can be used as fuels directly.

Figure 3: Octane structure

How can we make fatty acids? One way (though, I have to admit, not necessarily the best way right now) is to use E.coli. E.coli make fatty acids through a process that I can explain using the comic. Fatty acids, like the warrior’s sword, start out small. They begin as the two carbon compound acetyl coA.

Figure 4: Acetyl coA

E.coli (and many other organisms including you) form acetyl coA by breaking down glucose and other sugars. You can think of these sugars as the monsters (the mini-skeleton and the lizard thingy) attacked by the warrior in the comic. As bacteria break down glucose using a bunch of enzymes, they acquire energy from it. One of the products of this break-down process is acetyl coA. Acetyl coA can be used for a number of things. It can even be broken down further for more energy. Alternatively, bacteria can use some of the energy they get from glucose to combine multiple acetyl coAs to form fatty acid precursors called fatty acyl CoAs. Each acetyl coA added increases the size of the growing fatty acyl CoA by two carbon units (figure 5).

Figure 5: Adding acetyl coA onto a growing fatty acid (fatty acyl coA) increases its length by two carbons*

Enzymes adding acetyl coA onto octanoyl coA to form decanoyl coA

*Caution: Despite the stars, enzymes are not magical, they follow physical laws and simply help speed up reactions… the stars are just here to indicate that there’s more going on here than I’m letting on.

Just as the warrior uses the energy to make the sword bigger, E.coli can use acetyl CoA and the energy they get from glucose to make longer and longer fatty acids. E.coli use these different fatty acids to modulate the properties of their cell membranes (layers of molecules that separate the inside of the cell from its surroundings).

In my work, I try to direct E.coli to produce specific length fatty acids with desirable fuel properties.

February 21, 2019

From the BiLOLogy archives: what’s really going on when I do experiments

This is the first post in a series that i’m calling “From the BiLOLOogy archives.” BioLOLogy was a blog that I created in grad school. My intention was to explain papers and lab life through comics. I won’t re-post everything from BiLOLogy, but this series will feature a few pieces I still like. Enjoy!

This post was originally published in October 2014 (my fourth year of graduate school).

The idea for this comic came from a night when a friend of mine drove me to lab so I could do something “really quickly” (nothing ever takes as long as you think it will in a lab).

As you can see in the comic, that night I was doing something biology researchers do all the time. I was taking bacteria that were resistant to a particular antibiotic and putting them on plates containing the antibiotic in addition to some food. In this case, the point of the antibiotic was to make it so only my bacteria could grow on the plate. The antibiotic killed other bacteria, but did not kill the bacteria I was studying because they were resistant to it.

This whole process consisted of little more than putting a bunch of clear liquid onto a plate and spreading that liquid all over the plate. On the face of it, as my friend comments in the comic (and did in real life), it seems like a very uninteresting process. However, this is true of a lot of the experiments I do. Most of my days consist of the following:

1. Mixing different clear liquids together

2. Putting white powders into those liquids

3. Adding slightly more opaque liquids containing bacteria to the clear liquids

4. Putting these mixtures into machines that shake, heat, or cool them. Usually this makes the liquids more opaque

5. Putting these mixtures into machines connected to computers and watching the computers spit out numbers

6. Destroying all the bacteria by mixing them with yet another clear liquid (bleach)

On the face of it, this could be very boring, but I certainly don’t think about it that way… if I did, I would probably quit. Instead, I spend my days thinking about all the things going on that I can’t see.

As you can see in the comic, when they are thrown onto the plate, the bacteria spend their energy destroying the antibiotic (or at least producing proteins that make them immune to it) and growing into colonies with MANY MANY individual cells (the cities in the comic). I then come along and subject the bacteria to a bunch of tests that determine things like how fast they can grow, what molecules they can produce, and how those molecules can be used. While I can only see these things through a bunch of numbers on my computer, they’re still awesome to think about!

January 21, 2019March 18, 2019

Viruses aren’t just for humans

Cartoon of phage attaching to a bacterium

You’ve probably lived through the woes of various viral infections. Viruses cause the common cold, the flu, warts, and more. You may know that bacteria cause some similar health problems, but did you know that viruses can infect bacteria too? In addition to killing countless bacteria, bacterial viruses (or “phages”) also make useful research tools. I’ll introduce you to some of the fantastic uses these tiny killers here.

Phages help researchers manipulate DNA

Phages survive by attaching to bacteria, injecting them with DNA, and forcing them to follow the instructions in that DNA. These instructions drive the bacteria to copy phage DNA and make more phages. The new phages then encapsulate the DNA and, eventually, there are so many DNA-filled phages that they explode out of the bacteria. Then they start the process again.

Cartoon of a phage attaching to a bacterium — A phage attaches to a bacterium and is ready to steal bacterial resources.

New phages occasionally grab up bits of bacterial DNA instead of phage DNA. If researchers know that one bacterial strain has useful DNA, they can use phages to encapsulate it. The phages will then deliver the useful DNA to other bacteria. These bacteria will follow the instructions in the useful DNA.

For instance, say you had one bacterial strain with a gene that made it really good at eating sugar and a second bacterial strain with genes that made it turn sugar into gasoline. You could use phages to put the sugar-eating gene into the gasoline-producing strain. The resulting bacteria could eat sugar and turn it into gasoline.

Using phages to control genes

When phages inject their DNA into bacteria, they need to make sure the bacteria follow the instructions encoded within it. To do so, some phages have molecular machines that force bacteria to devote themselves to following these instructions.

We’ve figured out how to use these same molecular machines to force bacteria to follow the instructions in researcher-specified DNA sequences. With these tools, we have more control over bacteria. For instance, we could use these tools to force our sugar-eating, gasoline-producing bacteria to do nothing but produce gasoline from sugar. These would be more efficient gasoline producers because they wouldn’t waste any energy on doing anything else.

Using phages as antibiotics

Because phages kill bacteria, we can potentially use them as alternatives to antibiotics. This may prove a bit tricky because, unlike current antibiotics, phages generally kill specific species of bacteria. As a result, we might have to make new phages for each new kind of bacterial infection we’d like to treat.

This specific killing could also be a benefit. Current antibiotics kill both beneficial and harmful bacterial species. Phage treatment may leave beneficial species intact.

As we learn more about bacteria and human health, I’m sure there will be many more developments in the world of phage research. Heck, a quick google search for “Phage biotech companies” clearly shows there’s interest in this area. If you’d like to learn more about phage, I’d recommend this cool episode of Radiolab (a podcast) or this quick New Yorker article.

January 14, 2019March 18, 2019

Teeny, tiny turkey basters, antibiotics, and problems with their funding

Just a few days ago I attended a free conference hosted by the Center for Emerging and Neglected Diseases at UC Berkeley. At the conference, attendees discussed ways to diagnose and treat emerging and neglected diseases – diseases that are on the rise or which research has left behind. At the conference I learned about one particularly huge problem in this field and about a ton of new research that gives me hope for the future.

What needs to change in emerging and neglected diseases: investment in diagnostics and antibiotics

You cannot effectively treat a sick person if you don’t what’s causing their sickness. This seems obvious but believe it or not we’re lagging behind in our ability to diagnose a number of diseases. For example, as I learned at the conference (and later fact checked on the WHO website), only 20% of the millions of cases of Hepatitis C were diagnosed in 2015. Being that Hepatitis C can have rather dangerous health effects including cirrhosis and liver cancer, this is clearly a problem.

Unfortunately, as new diagnostic tools will have some of their biggest impacts in poorer regions, they must be inexpensive. This means investors have less monetary incentive to back their development. There’s a similar problem in the world of antibiotics research. Despite the fact that antibiotic resistant bacteria are on the rise, new antibiotics won’t generate as much revenue as other drugs. Thus new antibiotics research won’t get funded until antibiotic resistance gets worse, demand for new antibiotics goes up, and prices increase.

The solution as discussed at the conference is to find ways to decouple the high costs of the diagnostic/antibiotic clinical development process from the cost of the final product. From what I could tell, this will require more philanthropic organizations, NGOs, and governments to grant more money to clinical development in these fields. For example, one awesome nonprofit at the conference, FIND, works to provide resources, funding connections, and research infrastructure to those developing diagnostics. We need more organizations like FIND and, in the absence of government support, donors who will fund this research.

Cool advances in diagnostics and antibiotics research

Despite the need to fix the funding environment, there are a lot of cool developments in diagnostics and antibiotica research! Here’s a smattering of things I learned about at the conference:

Cartoon of a nanopipette detecting a disease-associated toxin. — Conceptual depiction of a nanopipette with biological materials (purple) that can attach to disease markers (green skull and crossbones). See description below.

Tiny turkey basters for detecting disease – Pinpoint Science is a startup creating tools for diagnosing disease. They’ve developed a device that uses nanopipettes (basically teeny tiny turkey basters) to detect disease compounds (think toxins and parts of viruses). When biological materials in the nanopipettes attach to disease compounds, they cause changes in electrical signals that tell users the disease is present. Pinpoint believes that it can provide these devices at incredibly low prices (in the $1 range) and use them to diagnose all sorts of diseases.
Cell phone microscopes – Aydogan Ozcan from UCLA is working to develop cell phone attachments that turn your phone into a mobile microscope. These can be produced at much lower prices than standard microscopes. Thus they’ll make it easier for researchers all over the world to analyze biological samples. I imagine these could be great for people in the DIY Bio space as well.
Developing new antibiotics with a little help from out gut bacteria – Believe it or not, the “good” bacteria living in your gut defend you against disease-causing invaders. Indeed, these gut bacteria produce compounds that kill the invaders. Manuela Raffatellu from UCSD is studying these compounds. She hopes to use what she learns to create the next generation of antibiotics. I’m absolutely fascinated by this work and will hopefully write a separate blog post on it soon.

This is just a smattering of the research going on in the world of diagnostics and antibiotics. Researchers are coming up with many creative ways to diagnose and treat emerging and neglected diseases. We just need to fund them better!

November 25, 2018November 26, 2018

Bacterial Abilities in the Gut: Stealing Vitamin B12

Bacteria are cool. They can do all sorts of things that you might not normally think about as you kill millions of them with your favorite antibacterial soap. Some bacteria can break down and eat toxic wastes. Some bacteria can use sunlight and carbon dioxide to grow. Some bacteria can even be used to create medicinal compounds. Although we know a lot about what bacteria can do, we still need to learn a lot more in order to effectively solve the world’s problems. Bacteria are everywhere and will therefore somehow be involved or interact with any technique used to solve problems like global warming or disease.

Importantly for this post, it’s estimated that there are TRILLIONS of bacteria throughout the human gut and we are far from understanding all of the beneficial and dangerous things they can do. As a small but meaningful step in the right direction, researchers from Yale University recently discovered that bacteria in the human gut can grab and use vitamin B12 coming from our food. Essentially, these bacterial pirates can steal vitamin B12 that would otherwise be absorbed in the small intestine, but this isn’t necessarily a bad thing.

A bacterial pirate steals vitamin B12 from the human gut

To steal vitamin B12, these bacteria create a protein that latches onto the vitamin really tightly thus allowing the bacteria to pull the vitamin into their cells and use it for growth. While they may be pirating some vitamin B12 from us, these bacteria also don’t survive well in the gut if they lose the ability to steal from us. Given that these bacteria likely play important roles in helping us digest foods and maintain healthy mixtures of bacteria in the gut, we can forgive them a little bit of pirating.

Now that researchers know how these bacteria grab onto vitamin B12, they might be able to use this knowledge to prevent the bacteria from stealing B12 in humans who don’t get enough B12. They could also potentially use this information to create new therapeutic bacteria that are better at surviving in the gut. For example, if researchers wanted to engineer bacteria that could live in the gut and create a nutrient for us, they might give the engineered bacteria the ability to steal B12 so that they are better at surviving in the gut. The researchers could also make it so they could shut off the stealing ability. If things started to go wrong, the researchers would just shut off the bacteria’s stealing ability and they’d be eliminated from gut.

As you can see, many new opportunities have been opened up simply from learning a little bit more about what bacteria can do. At first glance, the ability to steal B12 from us seems like it must be a bad thing, but, not only does this ability help useful bacteria survive inside of us, it potentially gives researchers new ways to manipulate bacteria for beneficial purposes.

I’m hoping to write more about cool bacteria and all the things they can do in the future so stay tuned!

References

Wexler, Aaron G., et al. “Human gut Bacteroides capture vitamin B12 via cell surface-exposed lipoproteins.” eLife 7 (2018): e37138. Pubmed PMID: 30226189. PubMed Central PMCID: PMC6143338.