Biotech – TylerJFord.com

April 16, 2019April 16, 2019

Instagram story round up: Pig artificial insemination, clonal tree farming, and injecting viruses into the eye

Doodles of frozen pig sperm, clonal tree farms, and viruses ready to deliver DNA to an eye

Here’s a round-up of some of the stories from my SciCommByTyler instagram account. Follow me on instagram to see similar stories each weekday!

Pig sperm don’t freeze well

Many farmers use artificial insemination to breed their animals. This process involves injecting female animals with sperm from specific males. With artificial insemination, farmers can quickly breed their best male animals with many females. The result is many offspring with useful traits.

It is useful to be able to freeze sperm from high quality males. Such frozen sperm can be transported to other farms or stored for future use. This helps spread useful genetic traits.

Unfortunately, farmers don’t have super effective ways to freeze pig sperm. Many pig sperm die during the freezing process. Farmers still use artificial insemination for pig breeding. It’s just more difficult to store or transport pig sperm for extended use.

Scientists hope to overcome this problem with creative genetic engineering techniques. I’ll be writing more about this soon!

Growing cloned trees

Like all organisms, trees have DNA. Specific kinds of trees have specific DNA sequences that give them particular qualities. Natural forests are composed of many different trees with different DNA sequences. They are beautifully diverse jumbles.

In contrast, tree farmers often grow rows and rows of trees with identical DNA – tree clones. They do so because they want many trees with very specific characteristics. These characteristics make their wood valuable for particular uses. Clonal forests are beautiful in their own way.

Injecting viruses into the eye

Doodle of viruses ready for injection into an eye

DNA sequences encode cellular parts that give cells their functions. In some forms of blindness, altered DNA sequences encode broken parts. These broken parts can lead to progressive vision loss.

As I’ve written about before, viruses can deliver DNA sequences to cells. These scientist-designed DNA sequences can fix cellular parts and treat diseases.

It’s hard to get such viruses to some parts of the body. However, it’s actually quite easy to get them into the eye. Thus scientists can inject viruses with corrective DNA sequences into the eye and restore vision to some patients.

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.

March 26, 2019March 26, 2019

Pigs: the future heroes of organ transplantation?

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.

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!

October 31, 2018April 29, 2021

3 Effective Cancer Immunotherapies

You’ve probably heard that a lot of money goes into cancer research but haven’t heard enough about its impacts. Through a series of coincidences at work, I found myself reading quite a bit about cancer immunotherapy – using the human immune system to better fight cancer. I was astonished by how many effective cancer therapeutics are coming out of this field and thought I’d quickly describe how a few of them work here.

*A Couple of Quick Notes* – We need new cancer therapeutics because standard cancer treatments (things like surgery to remove tumors, radiation therapy, and chemotherapy) can damage our bodies in terrible ways and are often ineffective. Also, even though the therapies below have been successful in some cases, every cancer is different, and they won’t be successful for all types of cancers or even all patients with a particular type of cancer.

3 Types of Successful Immunotherapy

1. Adoptive Cell Therapy

Cartoon of a cell used in cell therapy There are many different types of cells in the immune system. These play a variety of roles in fighting disease causing agents (pathogens) like viruses, bacteria, and cancer cells (yes, our bodies naturally fight cancer). In adoptive cell therapies, scientists take immune cells out of our bodies, make the cells better at fighting cancer, propagate them, and then put them back into our bodies.

Before the immune system can begin fighting a pathogen effectively, the cells that do the fighting need to be told a pathogen is present and what it looks like. Dendritic cells do this by showing components of the pathogen to other cells in the immune system. In one form of adoptive cell therapy, doctors take dendritic cells from a patient, load them with cancer cell components, and put them back in the patient’s body where they can alert the rest of the immune system to the presence of the cancer.

For more information, read up on Sipuleucel-T, an FDA approved adoptive cell therapy for prostate cancer.

2. Antibody Therapy

Cartoon of antibody therapy You may have heard of antibodies. These are proteins that our immune systems naturally produce. Antibodies bind to pathogens and prevent them from causing disease. Through years of research, scientists have learned ways to produce antibodies that bind to cancer cells and slow cancer progression.

For example, some cancer cells produce a signal that tells the immune system to slow down and stop attacking them. Scientists have produced antibodies that bind to and block this signal. These antibodies have been proven effective at boosting the immune system and fighting a wide variety of cancer types.

For more information, read up on PDL1 inhibitors and watch this great video from Dana Farber.

3. CAR-T Cells

Cartoon of a CAR-T cell getting ready to attack a cancer cell. CAR T-cell therapy combines aspects of adoptive cell and antibody therapy. T-cells normally bind to and kill cancer cells, but can only do so if they have the appropriate binding proteins. In CAR T-cell therapy, doctors take T-cells from a patient and give them new proteins called chimeric antigen receptors (CARs) that are very similar to antibodies. CARs allow the T-cells to bind to cancer cells. Once put back into the patient, these CAR T-cells can be effective at binding to and fighting the cancer.

CAR T-cells are effective at fighting a few types of cancer and have completely cured some patients who were otherwise out of hope.

Read Up on CAR T-Cell Therapy.

October 31, 2018April 16, 2019

Why Viruses Are Great Gene Delivery Vehicles

Drawing of a cartoon virus delivering a piece of DNA Pretend that you’re a delivery person. Now pretend that you have all the packages you need to deliver today. You step out of your delivery truck onto the street. You’re ready to seize the day and start delivering with a smile on your face, but, just then, some crazed urge overcomes you. You want to do the worst job possible. How are you going to satisfy this urge?

If I wanted to be an absolutely terrible delivery person, I’d walk down the middle of the street and throw my packages everywhere at random. I’d probably end up throwing many packages into the street and into random yards. I’d probably hit some people and their pets. I might even get hit by a car. However, if I threw enough packages, at some point I might at least get one into the appropriate yard or driveway.

Like letters and packages, gene therapies need good delivery people. For gene therapies to work, healthcare providers need to successfully and specifically deliver genes to broken cells. Once in the broken cells, the genes produce things that help fix the cells thereby treating or curing disease. In a gene therapy for blindness for example, you might deliver genes to cells in the eye that make the eye better at detecting light (Connie Cepko’s lab at Harvard is doing this).

Unfortunately, if we just inject genes strait into our bodies, the gene therapy will function about as effectively as our crazed delivery person – they don’t necessarily get to the right place, they might be destroyed in the bloodstream, and they could cause further dangerous effects if they get into the wrong cells.

So what makes a good delivery person? A good delivery person carefully walks down the sidewalk (avoiding cars and stray dogs) and delicately places packages and letters into the mailboxes of their intended recipients. That’s all well and good for big ole letters and packages, but how do we go about delivering genes with such tenderness and care? Nature provides the answer – viruses!

Viruses as Gene Delivery People

You’re possibly looking at your screen a little skeptically and thinking, “Don’t viruses cause disease?” The answer is, yes they do, BUT, to cause disease, viruses often must deliver their own genes to cells. We now know enough about how some viruses work that we can strip them of their dangerous genes and, instead, get them to deliver therapeutic genes to cells.

Viruses are fantastic because many already deliver genes to specific cells (remember how HIV targets the immune system for instance). In fact, using our knowledge of how viruses work, we can even engineer them to deliver genes to new cell types.

Limitations of Viral Delivery

So, why haven’t we used viruses and gene therapy to cure a ton of diseases? Part of the answer to this question is that we’re only now beginning to understand enough about diseases, genes, and viruses to make effective therapies. In addition, viruses do have limitations. Here are a few:

Size – Viruses are very very small (way smaller than cells) and just can’t deliver all the genes we need to treat some complex diseases. This is like having a delivery person who is too weak to deliver all of your new Ikea furniture even though you know it will look awesome in your new apartment.
Lifespan – Some viruses deliver genes to cells and the genes do their jobs for a while, but then they stop working. This is something like your favorite movie going off of Netflix. It’s delivered to you for a while and you’re kept happy, but then you can’t watch it anymore for unknown reasons leaving you in pain.
Immune Responses – Some viruses used for gene therapy still have markers that tell the immune system that they’re dangerous. These can cause immune reactions that harm the patient. This would be like your delivery person dealing drugs on the side and getting confronted by the cops at your doorstep… you might get hurt in the exchange.
Integration Problems – Though some viruses are very good at getting therapeutic genes into cells, sometimes they put them in the wrong place or they put some of their own genes into the cells leading to further damage and disease. This would be like your delivery person occasionally jamming a package down your toilet without you noticing or accidentally dropping his pet cobra in your mailbox.

Different types of virus-based gene delivery systems have different combinations and levels of these limitations (some of the advantages and limitations of viruses used in research are discussed in this guide). It is therefore up to researchers to pick or engineer the right viruses to reduce these limitations for specific diseases.

Excitingly, we’ve learned a ton about how viruses work and you’re likely to see many virus enabled gene therapies coming out soon. Heck Voyager Therapeutics recently described promising results from their work developing a virus delivered gene therapy for Parkinson’s disease. So keep your eyes open – I’m sure there’s much more to come!

October 31, 2018October 31, 2018

3 Things I Learned Recently about Plant Biotech

Plants! We’ve been experimenting with them through farming and breeding for ages and we’ve had many successes (just look how corn has changed from its ancestral form for a great example). Nonetheless, more can be done to lower costs, increase variety, and improve nutrition (among other things). Here are just a few things I’ve learned about recently – engineering more stable animal feed, changing flower color, and making apples that don’t brown.

1. Making More Stable Animal Feed

Cheese burgers are delicious. However, to keep making cheese burgers, we need to keep making cows. A lot of money and resources go into making the tasty animals we eat (a good reason to be vegetarian at least some of the time) and farmers are always looking for ways to decrease costs.

Luckily, plant researchers have taken note. One way researchers are trying to lower farming costs is by making plants used for animal feed more stable. The plants we feed to animals often need to be stored prior to feeding and their nutritional components can degrade during storage. Scientists at the USDA are specifically altering alfalfa (apparently a component of feed) so that it produces chemicals that keep its proteins from degrading. This stronger alfalfa could some day lead to healthier, less expensive animal feed.

2. Changing Flower Color

Have you ever wanted a particular type of flower to come in a different color? Plant breeders have been changing flower colors for years by crossing different varieties together. The process of altering the genes present in a particular plant (really what you’re doing in plant breeding) may be more straightforward and controllable if performed using genetic engineering techniques.

Toward this end, researchers recently used the genetic engineering tool, CRISPR, to change the Japanese Morning Glory from violet to white. This specific color change isn’t groundbreaking as there were already white Japanese Morning Glories, but it shows that CRISPR can be used to quickly get a desired color if we know enough about the underlying biology.

The company Revolution Bioengineering is doing something perhaps a little more exciting – they’re making flowers that change color overtime. I’m intrigued to see how things turn out!

3. Marking Non-browning Apples (Arctic Apples)

I often find myself cringing before taking a bite out of a brown apple slice that’s been out for too long so I was excited to discover that the company Okanagan Specialty Fruits makes genetically modified, non-browning apples (see description on their blog). They call them “Arctic Apples.”

Apparently these apples have been in production for a while but they’ve only been sold in the U.S. since early 2017. Full disclosure, I haven’t eaten them yet and can’t vouch for their taste, but I’d love to try them out.

There’s all sorts of other stuff going on in the world of plant biology and I’m hoping to touch on some fancy things like plant metabolic modeling and engineering carbon fixation in later posts. Stay tuned!