Epigenetics: The New Buzz Word In Cancer

Cancer is caused by mutations that either turn on the expression of oncogenes or turn off the expression of tumor suppressors. Oncogenes are elements that promote growth and cell division while tumor suppressors slow down the cell cycle and work to keep the cell from dividing. In a normal cell, there is an interplay between the two to ensure that cells only divide when it is necessary. In cancer cells, cell growth is rampant and out of control. How does a cell turn on an oncogene or turn off a tumor suppressor? In the past, we’ve always assumed that there was DNA damage. A mutation could happen in a gene that either keeps it from being expressed or alters its subsequent protein to make it be constitutively active. Are there other ways in which cancer can arise?

I sat in an interesting lecture yesterday regarding the epigenetics of cancer. Epigenetics defines changes in gene expression that cannot be explained by DNA damage or alteration. DNA is bundled in the cell nucleus by winding around histones to make it more compact. These histones have tails that can be modified in order to make the DNA more open and available for gene transcription or more compact and silenced. The genetic code is comprised of four bases, of which cytosine can be methylated leading to DNA silencing. Changes in gene expression can occur epigenetically to cause expression of oncogenes where they should not be or silencing of tumor suppressors where they are desperately needed.

Epigenetic changes in cancer are a current “hot topic” in research, and there is a lot that needs to be studied. When it comes to DNA mutation, there are many checks and balances to keep changes from being passed on to the next generation of cells. Occasionally, a mutation makes it past the DNA repair mechanisms, and this can lead to pre-cancerous changes. However, there are no checks and balances with epigenetics. The expression levels of genes must be more fluid and ever-changing in order to give rise to so many different tissues and organs in the human body. The DNA sequence is the same between the heart and the brain. However, there are vastly different epigenetic gene expression profiles between the two organs. During development and even during the lifetime of a cell, gene expression needs to be able to subtly shift depending on the environment and destiny of the cell. Therefore, it is easy to see how mutations in the epigenome can occur much more easily than mutations in the nuclear genome.

What is to be the next focus of scientists studying the epigenetics of cancer? Currently, scientists are scanning the epigenome of many thousands of tumors in order to get a good picture of which tumors have which changes. Just as it is with DNA mutations in which some genes are mutated much more in one cancer over another, such as the BRCA1 mutation in breast cancer, scientists are finding similar results in the epigenome. Finding such  pattern in the epigenome will give scientists a jumping off point for further research into cancer treatments. 

“Breast Is Best”… But Why?

Bodily fluids are some of the most studied parts of a human. I’ve only been in science a few years, and in that time, I’ve done more experiments with blood than I care to remember. Even as an undergraduate we learned the sophisticated techniques involved in testing our own urine. Now THAT was pleasant right after breakfast! While I personally haven’t done tests on saliva or spinal fluid, others in my labs were experimenting with these. However, there’s one bodily fluid that is sort of the “uncharted territory” of the body: human breast milk.

breastfeedWe’ve all heard the colloquialism “breast is best” when referring to how to feed your infant. Studies have even shown that breast-fed infants are more likely to survive than bottle-fed. Most people think only of the antibodies that pass from mother to child to boost the newborn’s immature immune system.   Breast milk also contains immune cells such as macrophages that help to engulf dangerous bacteria and foreign particles. What else does breast milk supply?

Breast milk is first and foremost, milk: a source of nutrition. It is a complete meal full of carbohydrates, fats, and proteins. Interestingly, though, many of the oligosaccharides in breast milk cannot be broken down by the infant’s digestive tract. So, the question to ask is “who is actually digesting and benefitting from the breast milk carbohydrates?” The obvious answer would be the gut microbes that make up the intestinal flora. In 2006, however, a study was done in which researchers fed breast milk to several species of bacteria that commonly inhabit the intestinal tract. None of the bacteria lived, as they were unable to digest the milk.

After several more tests, one type of bacteria was found to digest breast milk: Bifidobacterium longum biovar infantis (or as I will refer to it, B. longum bv. infantis). What sets this bacterium apart from all of the rest? Genome studies of intestinal flora bacteria found that B. longum bv. infantis was the only species to have the ability to produce the enzymes needed to break up breast milk. After studying infant intestinal flora, researchers found that this bacterium makes up about 90% of the population of the gut. While it is not known how the bacteria first inhabit the gut, whether it is picked up by breast milk or during birth, one thing is for certain: it overtakes everything else! Adding more fuel to the fire that this bacterium is important in the infant gut, researchers have found that only about 3% of the adult gut is inhabited by this bacteria. That’s a striking difference!

What could be the reasoning behind these seemingly important bacteria inhabiting the intestine of an infant? Researchers postulate that the bacteria and humans probably coevolved. By having only one type of bacteria that can digest breast milk, the bacteria is able to starve potentially pathogenic bacteria and keep them from thriving and causing illness in the baby.

So, will medicine move to produce probiotics for infants to take if they are unable to be fed breast milk? Unfortunately, I’m not sure this is the answer to the problem. Even after feeding probiotics, the bacteria would not have the beneficial nutrients from the breast milk in order to survive. Sure, they would have formula from which to derive their nutrients, but they would not outlive and outpace every other bacteria in the intestinal flora as these could also take nutrients from formula.

Article Source: Trisha Gura. “Nature’s First Functional Food”. Science. Vol. 243 no. 6198. Pp. 747-749. 15 August 2014

Image Source: Jason Carter. “On the Boob” 22 July 2008 via Flickr. Creative Common Attributions

Who (Or What) Is In Charge Of Our Food Cravings?

Has anyone ever tried to trick you by asking “What is the most populous cell in the human body?” More than likely, the person asking this was a young child, as they always seem to find quirky questions like these the funniest. After digging into the back of your brain for something that you probably learned in elementary school, you may come up with a very reasonable answer: red blood cells. However, this answer to the child’s joke would be wrong. The child cleverly answers back “Actually, they aren’t cells made by the human body at all! They are the bacterial cells that inhabit our guts!”

bacteria

True, the bacteria that reside in our intestines are on the order of 100-fold greater in numbers than any other cell in the body. This begs the question of if they have any influence over the workings of our bodies. We know that the bacterial cells are important to our digestion and live in a symbiotic relationship with ourselves. Recent studies are showing that the bacteria also play a role in our appetites and our cravings. How can such tiny organisms have such great influence?

Scientists have only recently begun to appreciate the magnitude of the bacteria in our gut and the interplay between us and them. Because our digestive tract is intimately connected with our bloodstream and our lymphatic system, it is possible that bacteria release chemical signals that can travel to our brains and influence the types of foods that we next choose to eat. Bacteria are also known to produce toxins after certain foods are eaten that cause us to feel ill. This will definitely influence our choices in the future! Even more interesting is research involving the vagus nerve. This is the 10th cranial nerve that enervates the stomach, providing a direct connection between the digestive tract and the brain. Scientists believe that bacteria can produce chemicals that act upon the brain through this conduit, too!

The composition of the bacteria in our guts differ based on the foods that we eat. Some digest sugars more readily while others prefer fats. Some are even as specific as to digest cultural delicacies that are only found in certain parts of the world (and therefore, only the guts of those living in those regions). As our diets change, so do the bacteria in our intestines. Future endeavors for scientists will be to investigate changing diets and the incorporation of probiotics to alter the bacterial flora. Will this cause cravings to change? Only time will tell.

Article Source: University of California, San Francisco (UCSF). “Do gut bacteria rule our minds? In an ecosystem within us, microbes evolved to sway food choices.” ScienceDaily. ScienceDaily, 15 August 2014.

Image Source: PNNL. “Improving Human Intestinal Health” 26 September 2012 via Flickr. Creative Commons Attributions.

With Exercise, More Is Not Always Better!

If you’re anything like me, you work diligently to fit daily exercise into your routine. I try to run at least a few times a week, and I try to get in my 10,000 steps every day. I’ve trained for several half marathons and have even been determined enough to train for and run a full marathon once. Sometimes, I wonder if I’m doing enough. What about those people who run several marathons in a year? Those people who run up to 100 miles a week? If there’s a certain prescribed amount of exercise that we should get a week, then shouldn’t more be better? For your reference, the current advised amount of exercise is 150 minutes per week of moderate exercise (think: going for a walk after dinner) or 75 minutes of intense activity (think: running after work).  Are these people who exercise as much as their time allows healthier than I am?runner

Scientists recently followed a cohort of people who had survived heart attacks and were currently engaging in daily exercise. Because the people did different types of exercise, the scientists used a formula to equate the efforts exerted. For example, if one person was a runner and the other was a walker, the walker would obviously have to walk further in order to get the same benefits as the runner. The results showed that as long as the people were running less than 30 miles a week (an equivalent to walking less than 46 miles a week), they had a 65% decrease in death due to cardiovascular trauma. However, more exercise proved to increase the risk of death. Even more striking, the preponderance of a cardiovascular event leading to death sharply increased with each incremental uptake in the amount of exercise. In layman’s terms, if someone was running more than 30 miles per week, the likelihood of death due to a heart attack or other cardiovascular event sharply increased with each extra mile run.

The one caveat to this study was that the cohort was heart attack survivors, not the general population. However, the scientists did note that there competitive running events and other events of similar caliber also had a higher incidence of death due to a cardiovascular event as opposed to more relaxing sports.

So, what advice should we take from this study? Exercise. Not too much. Not too little. And be sure to get a rest day in here and there!

Article Source:

Elsevier. “Contrary to popular belief, more exercise is not always better.” ScienceDaily. ScienceDaily, 12 August 2014.

Image Source: Alan Hood. “Male Runners”  9 September 2008 via Flickr. Creative Commons Attributions.

We’ve Arrived — At Last!

This week, the European Space Agency’s Rosetta spacecraft finally arrived at comet 67P/Churyumov-Gerasimenko after a decade-long journey. Why did it take so long to arrive at the comet, which is located just between Mars and Jupiter? Flying in space is quite a bit different from driving your car on Earth. For one thing, there are no gas stations in space with which to refuel your spacecraft. Scientists need to come up with the perfect trajectory that will get a spacecraft to its destination using only the fuel available at launch. At this time, no rocket can carry enough fuel and still be light enough to propel Rosetta all of the way to the comet. Therefore, Rosetta had to use gravitational boosts from the sun, Earth, and Mars by doing multiple fly-bys to gain enough speed and the appropriate trajectory to rendezvous with the comet.

Rosetta

Now that Rosetta is circling the comet, the real experiments of the mission can begin. Comets have a distinctive tail of dust and gas that are blown off of the comet’s nucleus by the sun’s energy. One experiment will be to study this tail and see how it changes as it nears the sun while another will study the bright gases encircling the comet in its entirety. Finally, in November 2014, Rosetta will send a lander down to the comet to study it from within.

Why did scientists go through all of this trouble in order to study a comet? The mission obviously took many years of planning and maneuvering just to get to the point where the spacecraft and the comet rendezvoused. Comets are some of the oldest objects in the solar system. They can originate from the furthest edge of the solar system. Even though this mission seemed quite difficult and intense, it is much less so than traveling to the edge of the solar system. Studying a comet as it approaches the inner planets gives us a glimpse of what the outer reaches of the solar system contain.

 
In this same line of thought, my brain went to the Voyager spacecraft, which are the furthest manmade objects from Earth at this time. Have they reached these outer edges of the solar system from which comets arise?

Oort

Comets come from two regions of the solar system: the Kuiper belt and the Oort cloud. The Kuiper belt is the origin of the short-period comets, such as the one that Rosetta is orbiting. The Kuiper belt is a donut-shaped region that extends just beyond Neptune. The Voyager spacecraft have been in the Kuiper belt. The Oort cloud is much further and can really define the edge of the solar system. This is a large shell of billions of comets and other icy remnants of the early solar system. So, the question is “Where is Voyager 1, the furthest spacecraft?” Because of the large expanses of space, Voyager 1, while it is said has left the solar system, has only left the heliosphere. However, it has not even entered the Oort cloud. The answer to when Voyager 1 will exit the solar system and leave beyond the Oort cloud is estimated to be about 14,000 to 28,000 years from now!

 

Article Sources:

http://science.nasa.gov/science-news/science-at-nasa/2014/06aug_rosetta6/

http://www.esa.int/Our_Activities/Space_Science/Rosetta/The_long_trek

http://solarsystem.nasa.gov/missions/profile.cfm?MCode=Voyager_1&Target=Beyond

 

Image Sources:

DLR German Aerospace Center “Landung von Pilae auf dem Kometen” 14 January 2014 via Flickr. Creative Commons Attributions.

NASA Goddard Space Flight Center “Solar System, In Perspective” 12 September 2014 via Flickr. Creative Commons Attributions.

Sperm That Attacks The Female? Say It Isn’t So!

Growing up in the Midwest, it was common knowledge that if you have a horse mother and a donkey father that the offspring will be a mule. Mules, however, are sterile creatures. This stems from the fact that a horse has 64 chromosomes and a donkey has 62 chromosomes; therefore, the mule is a mixture of the two with 63 chromosomes. When a mule goes to mate, chromosomal misalignment occurs and the embryo will not be viable. This is the normal course of interspecies breeding.

Today, I read a very interesting article about interspecies breeding of worms of the genus Caenorhabditis. In this experiment, researchers took worms of different species to see what the mating outcome would be. Unlike the mule story from above, no offspring were produced. More strikingly, the females were sterilized after mating with a different species and oftentimes died as a result. What could cause such a drastic result in the worm?

Elegans

Using fluorescently stained sperm from one species, scientists imaged a female worm from another species after mating. They found that the sperm were bursting through the uterus and attacking the ovaries! Not only that, but some of the sperm were even traveling through her entire body, causing tissue damage and eventual death!

Scientists believe that what they’ve termed “killer sperm” arise from a difference in agility between the species. When a male mates with a female, he may not be the only one; therefore, his sperm need to outcompete the rest in order to fertilize the eggs. Some species may have evolved to have stronger and more virulent sperm. In this case, if that male were to mate with a female that had not also evolved to withstand such an attack, his sperm would cause damage to the female’s body. Interestingly, they found that females who were accustomed to “gentler sperm” had ways to sense and avoid males with “killer sperm.”

I was glad that this study used “killer sperm” in both females that mate with other males and females that mate with themselves (hermaphrodites). I would have liked to see the opposite: females with the stronger uterus that is made to withstand the “killer sperm” mated with males with “gentler sperm.” Would they be able to mate and produce offspring? Or, is there another mechanism in these females preventing such embryos from being viable?

Article Source: University of Maryland. “‘Killer sperm’ prevents mating between worm species.” ScienceDaily. ScienceDaily, 29 July 2014.

Image Source: AJ Cann. “Caenorhabditis elegans” 4 December 2008 via Flickr. Creative Commons Attributions.

“Sixth Mass Extinction Event” Beginning?

When I was a child and went to the zoo, my favorite habitat to encounter was the African grasslands. From my favorite, the large, slow, lumbering elephant, to the more agile zebras, these animals never failed to capture my attention. What would we do if these animals were no longer on Earth? Would that affect our day-to-day lives or would we just have a less-than-stellar trip to the zoo?

Elephant

A recent story published last week detailed some of the cause and effects linked to what researchers are terming the “six mass biological extinction event.” We’ve all heard of such animals as the dodo bird becoming extinct, but I was astounded to learn that over 300 land animals had become extinct in the last 500 years. Probably less surprising to you is the fact that this is not because of a large meteor hitting the Earth as probably happened when the dinosaurs became extinct. Unfortunately, this decline in animal numbers has mostly been attributed to human encroachment and industrialization.

The animals that are at the most risk currently are the large animals of the African continent. Larger animals have longer gestations and smaller birth numbers, so as some animals die, it becomes more and more difficult to keep pace. Subsequent consequences to the endangerment of these animals include an increase in the number of small animals such as rodents taking over their living areas. Rodents carry many parasites and are host to several diseases that can infect other breeds and humans; as their numbers increase, infection rates are sure to increase, too!

Not only are the large animals impacted by human interference, but scientists have also seen a decline by nearly 50 percent in invertebrates such as insects and worms. What would happen if these animals became extinct? Insects are essential to the world crop and food production, as they are needed for pollination. Worms help to fertilize the soil in which the crops are planted. Without these species, there could be large and widespread impacts on human food production.

We need to think outside of the obvious when it comes to animal extinction. Sure, losing any species would be unfortunate, but there are wide-reaching consequences of just one or two species being eliminated. At the rate we are going with hundreds of species going extinct in the last half century, this really could be a mass extinction event. I only hope that the last 500 years are not indicative of the next.

Article Source: Stanford University. “Biologist warn of early stages of Earth’s sixth mass extinction event.” ScienceDaily. ScienceDaily, 24 July 2014.

Image Source: Jim Frost “Elephants 2” 19 October 2013 via Flickr. Creative Commons Attributions.