Synthetic enzyme, weight loss miracle

Obesity is a huge problem worldwide, costing our healthcare systems billions of dollars every year. The World Health Organization estimates that about 1.2 billion (yes, billion) people around the world are overweight, and among those between 200-300 million are clinically obese.

Figure 1: Obesity in America, courtesy of the New Yorker

Obesity is a tough health problem because it's existence can exacerbate a whole variety of other medical disorders. From type 2 diabetes to cardiovascular problems, the list is pretty large. Curing this epidemic would not only mean a healthier world, it would remove a huge burden on our hospitals as well. Well it seems like that cure may be upon us thanks to some obesity researchers from the Helmholtz Diabetes Center in Munich, Germany!

In a recent paper published in Nature Medicine, investigators have created a pretty incredible weight loss drug that reduced weight in laboratory mice by a third while preserving their lean muscle. Their strategy was a classic tour-de-force of synthetic biology: inspired by nature, improved by man.

There are three enzymes involved in this story: GLP-1, GIP, and Glucagon. The first two enzymes are used by the body to help control appetite and blood glucose levels, while the last enzyme is used to increase glucose in the blood. While increasing blood sugar may seem like a bad idea, it actually does assist with burning fat. In obese patients, the ability to respond to these enzymes is dampened. This is also why losing weight after being overweight for a while can be quite difficult - your actual biochemistry changes to make it tough!

Strategies using these enzymes individually have had limited success, so to circumvent this biologists engineered a molecule that displays characteristics of all three. As you can see from the graph below, the results are pretty remarkable.

Figure 1: A chart showing weight loss in mice. The black line is the control while each other line represents a different form of the drug. The most dramatic loss is seen when the highest concentration of drug was used!

So there you have it, yet another way in which synthetic biology is changing our lives. While we have yet to see this drug used in human patients, I think it's safe to say that we should be seeing more news out of this team in the near future!

In the pursuit of a cell-fie: Part 2

2014 has been one of the craziest years for science. We even landed on comet, for God's sake! Needless to say, this year has been pretty kind to the biological sciences as well, with some key innovations being made in the pursuit of an artificial cell. So sit back, relax, and let's go over some key innovations that have been made this year! You've got to move it move it

Researchers this year from Technische Universität München published a pretty cool paper in Science where they constructed artificial vesicles that could move on their own. Pretty amazing! To achieve this, they coated the inner surface of the vesicles with proteins called microtubules, which are the proteins that allow your cells to move (they also provide structure in what is known as the cytoskeleton. They also added motor proteins called kinesins that move microtubules, pushing the little cells forward. Of course, the energy molecule ATP was also added as fuel and BOOM! We have movement!

Figure 1: A high resolution photo of the artificial cell! Via TUM

And here's a cool video of the cells moving:

http://www.youtube.com/watch?v=Rc3Ss30z1Os

Part 3 is just around the corner! See you all in a few days!

In the pursuit of a cell-fie, Part 1

Have you ever taken time to look up at the night sky and gaze in amazement at the web of stars in the sky? Nature has the uncanny ability of inspiring a sense of wonder and awe when you sit down and wonder, "Gee, how does it all work?" I would argue that you'd probably get that same sense of wonder if you sat down and thought about the endless list of processes and reactions that your body has to undergo everyday just to keep you alive. There are about 37.2 trillion cells in the human body, with thousands of different functions represented in the various tissues. That's 372 times the number of stars in the Milky Way! When you consider that these cells must all interact with one another and look out for their own survival, you can see why constructing a completely artificial biological organisms would be pretty challenging!

Figure 1: The Milky Way

To make this task more feasible, scientists for many years have been trying to start with the cell, the smallest functional unit of life. Biologically speaking, a living cell must meet certain criteria that are rather difficult to fulfill artificially.  These are listed here:

1. Homeostasis: A cell must be able to regulate its own internal environment

2. Metabolism: A cell must be able to turn chemicals into energy

3. Adaptation: A cell must be able to response to stimuli from the environment and response appropriately

Stretch goals:

4. Reproduction: A cell must be able to replicate itself

5. Organize: Ideally, artificial cells would eventually organize themselves into more complex things like tissue and organs

6. Grow: Through metabolism, cells should be able to grow in size (or at least replicate to make the organism bigger)

Figure 2: The goal - are you up to the challenge?

If I gave you a laboratory and some supplies, could you do it? It certainly seems like a herculean task! Thankfully, researchers around the globe are hard at work to make such technology a reality. The journey to create an artificial cell dates back to the 60's, where Thomas Change at McGill University created a cell with an ultrathin membrane made of nylon and other crosslinked proteins, which contained a slew of things such as hemoglobin and various enzymes.

In the 1970's, this technology was revamped to make a completely biodegradable cell, and in 2011 researchers at Harvard University reported creating the first fully synthetic cell membranes.

The genesis of synthetic cell membranes marked an important step in crafting a fully artificial cell, but the issue of an artificial genome (collection of genetic material) still remained. Artificial DNA synthesis has been around for a while (I'll cover this in another blog post), but it took until 2010 for researchers at the J. Craig Venter institute to create a cell with a fully artificial genome. I'll spare you the minute details, but workflow of the experiment is as follows:

1. Design a genome on the computer.

2. Synthesize that genome artificially. In the case of the above experiment, the genome of a bacterium known as Mycoplasma mycoides was designed on the computer and crafted.

3. Insert the genome to a different cell. The researchers transplanted the M. mycoides genome into a different bacterium, M. capricolum.

4. SUCCESS!

Their M. capricolum began only producing protein products from M. mycoides, proving that their genome switcharoo was a success. The cells were even able to replicate, a triumph for the field! So as a proof of concept, humans can design fully functional artificial genomes. Done and done!

Note, however, that although the genome is artificial, we are still relying on the native bacterial machinery to translate those genes into proteins. Ideally, every part of these cells would be completely manmade, but it's clear that our foray into the creation of artifical life is having some success! In recent years (especially in 2014), huge advancements have been made in these other areas of cell creation. To see how biologists have figured out how to make cells move and carry out their own reactions, check out part 2 of this blog series on Monday!

Nature, improved

The vast majority of you who read my blog are probably aware of my obsession (a strong word perhaps, but apt) for science: wake up, eat, science, sleep, repeat. As a result of both curiosity and my natural tendency to wander the internet, I tend to focus my energies on learning things within a specific area due to an article I read or something of that nature. I call these "kicks", and for the next few blog posts I'm going to introduce you to a recent obsession of mine: synthetic biology.

Figure 1: Obligatory futuristic depiction of your DNA!

For centuries, humans have had to operate within the confines of nature. Want to cure your fever? Find an herb. Want to have bigger cows? A combination of careful breeding and finger crossing should do the trick! Now when we're faced with a problem (say, why don't we have better cancer-fighting enzymes), we are presented with a third option: make it up. We now have the power to craft our own custom DNA, create new cells, and effectively "edit" life as we know it.

Will these technologies be known to history as man's triumph over the universe, or will they be our downfall? I'll leave that for the ethicists to decide, but you can't deny that these technologies are pretty interesting! So stay tuned for some background into synthetic biology and where our technologies are at in 2014. You don't want to miss it!