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

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

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

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.

Pigs: the future heroes of organ transplantation?

Drawing of a pig superhero

Way back in 2017, I wrote a post about how scientists might one day use pigs to grow human organs. These “human-pig chimeras” could provide replacement organs to people with diseases like diabetes.

I recently learned that researchers are also trying to make pig organs suitable for transplant into humans. Their work doesn’t rely on putting human cells in pigs; they don’t need to make chimeras. Instead, these researchers use genetic engineering techniques to make pig organs more acceptable to the human body. Their modifications prevent the immune system from attacking and rejecting the pig organs. Thus, they hope to make pigs the future heroes of organ transplantation.

This research holds a lot of promise for patients in need of organs. Yet, it’s reasonable to worry that we devalue pigs by using them to produce human organs. My take is, if we accept pigs are sources of food, we should accept them as sources of organs. Nonetheless, I believe that we should develop transplant and food systems that don’t rely on living animals. Learning how to grow organs in pigs may help us move in this direction. Hopefully, we’ll eventually know enough about organ development to simply grow organs (and meat for consumption) in the lab.

Caricature of a pig pancreas
One day we may be able to transplant pig pancreases (pigcreases?) like this to patients in need.

Receptors – critical biological parts hijacked by viruses

“Receptor.” It’s yet another bit of biological jargon. It sounds like receptors should be small spacecraft launched to defend an alien mothership. Or maybe receptors are courtly underlings who receive guests before their presentation to the queen? In truth, receptors are cool and important biological structures that reside on cell surfaces.

As you might remember from my post on cell membranes, the layers of fat that surround cells are quite complex. They are studded with proteins that perform many functions. Some of these proteins are receptors.

Receptors all detect stimuli and cause cells to respond in some way. Often, receptors grab onto specific molecules floating nearby. Then they signal to the cell that they’ve done so.

The exact cellular response to a receptor signal depends on the receptor and on the stimulus detected. Some signals cause cells to grow. Others cause cells to move. Still others coordinate behaviors among many cells. Receptors are critical for many of life’s complicated processes.

Unfortunately, receptors have a darker side too. Many viruses use receptors as handles. With a good hold a on receptor, a virus can barge into a cell. Thus viruses hijack receptors to infect cells and cause disease.

Drawing of a virus grabbing onto a receptor to infect a  cell.
A virus grabbing onto a receptor to infect a cell.

Using receptor biology to prevent viral infection

Interestingly, scientists are using receptors to fight viral infections. They reason that, if they get rid of receptors used by viruses, the viruses will have no way of infecting cells. Many receptors are only important under specific circumstances. Thus, getting rid of them will have some small negative consequences, but the benefits of resisting viral infection are worth it.

Indeed, a scientist in China recently claimed to have modified babies to make them resistant to HIV (these are the so-called “CRISPR babies”). This scientist used a genetic technique to delete one of the receptors hijacked by HIV. The researcher performed this technique in embryos. Thus all the modified babies’ should be able to pass their modifications to their offspring.

What this scientist did was foolish for many reasons. Some of them include:

  • It is unclear if the technique was safe.
  • It is unclear if the technique accomplished its goal.
  • There are effective ways to prevent HIV transmission that don’t require this technique.
  • Some types of HIV use other receptors. Thus, the children won’t be protected from all types of HIV.

On top of all this, the scientist’s use of this technique raises many ethical questions. Most of these stem from the fact that the babies can pass on their human-designed modifications to their offspring. Should we modify the human gene pool in this way? Do we know enough about the potential consequences? Can we use similar techniques to do more than treat disease? Society at large must face all of these questions before we decide to use any similar techniques again.

This unfortunate work aside, other techniques modify receptors on adult cells. Future generations can’t inherit the modifications. Thus we can use these techniques following standard regulatory rules. Indeed, clinical trials using modified adult cells to treat HIV have had very promising results! Scientists can also give immune cells receptors that make them better at fighting cancer (see my previous discussion of CAR-T cells in this post). Receptors play a role in so many biological processes that we’ll likely see many more cool uses of them soon!

The next time you see a picture of smooth, round cell, remember that it’s studded with receptors and they do a lot!