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Molecular Biology in the Information Age

November 14, 2013

by Mariano Alvarez

There’s a revolution happening in biology. You’ve probably already heard about it, at least in part. Maybe you’ve heard the doctor on TV talking about personalized medicine. Or the commercial that promises to sequence your DNA. Or the news article about something called epigenetics. Those are all pieces of it, but it’s bigger than any one of them. Advances in molecular biology have changed the way that scientists can collect information, and it’s changing the way that we think about the study of life.

To explain why, I’ll start with a little history. Before the mid-1990s, looking at organisms on a molecular scale was difficult, time-consuming, and expensive. Scientists had to use complicated, costly procedures to get even the smallest bits of information about the genes and proteins of an organism. You might remember the Human Genome Project – it took ten years just to figure out the whole DNA sequence of a human being. And forget about taking this kind of thing outside – molecular techniques were often reserved for tightly controlled laboratory studies.

Today, we can sequence a whole genome in a single day. And instead of costing $3 billion, as the Human Genome Project did, it costs a few thousand dollars. Because molecular techniques like sequencing are now available to everyone, everyone is doing it – which means we have an explosion of new information. And with all of this new information, we can start to draw new conclusions. So instead of looking at the effect of a single gene, we can look at the effect of a whole network of genes together. Instead of just seeing how a protein works, we can look at how it interacts with all of the other proteins in the cell. We can even put these layers together by looking at all of the proteins and genes at the same time. When we can see all of these layers of interactions together across dozens or hundreds of individuals, we start to see emergent patterns and processes that would have otherwise been invisible.

The molecular revolution is already bearing its first fruits. The Human Genome Project has given way to the 1000 Genomes project, which aims to identify small changes in DNA across one thousand individuals. The ENCODE project is an even more ambitious venture, seeking to catalogue every functional piece of the human genome with the help of cutting-edge molecular techniques. And the focus isn’t solely on humans – the boundaries of plant biology, for example, are being pushed by efforts to catalogue molecular elements and pathways in Arabidopsis thaliana, a well-known model for plants. Efforts like these are the first crucial forays into the new world of molecular biology, where the combination of information and technology reveals a microscopic landscape as complicated and intricate as the macroscopic one.

The Unknown Potential of Ashwagandha a.k.a. “Horse Sweat”

November 7, 2013

Guest post by Jessie Alwerdt

The unknown mechanisms and lack of evidence of traditional medicine leaves a lot of room for criticism. With further research, there is the potential to uncover what the exact mechanism is in some of the plants used in traditional medicine. These plants may, therefore, be potential new targets for therapeutic drugs.  One particular plant that has gained a lot of interest of the last few years is Withania somnifera, also named Ashwagandha. Ashwagandha is a plant that contains phytochemicals. Phytochemicals (plant compounds) are non-essential for human survival, but many have been found to be beneficial to one’s health. The majority of research involving Ashwagandha revolves around the plant’s ability to reduce oxidative stress and its ability to suppress tumors but has been limited to animal studies1,2  The most compelling research involves its use in treating or preventing Alzheimer’s disease (AD)3.

One of the hallmarks of AD includes the build-up of amyloid plaques. Amyloid circulates through the peripheral nervous system then passes through the blood-brain barrier (BBB), which regulates what enters the brain. After passing through the brain, it circulates back out through the BBB back into the peripheral nervous system as a continuous cycle. When this amyloid becomes larger and begins to misfold, the amyloid can no longer circulate through its normal cycle. This can cause amyloid build-up in the brain3. With the oral ingestion of Ashwagandha in mice with Alzheimer’s disease, there was indication of decreased amyloid plaques in the cortex and hippocampal region. Additionally, there was proper clearance of amyloid through the BBB. The results of the study suggested that Ashwagandha had the potential to break up amyloid that circulates through the BBB by targeting β oligomers, which are smaller forms of soluble amyloid that is a precursor to the larger, more harmful amyloid fibrils4. Drugs that target the BBB are great candidates for AD interventions.

As researchers begin to uncover more pieces to the puzzle to what causes AD, there is a greater understanding that there is much more going on in the body as a whole than just build-up of plaques in the brain. With more research and additional clinical trials, plants commonly used in traditional medicine, such as Ashwagandha, may hold the key to the prevention or treatment of AD.

JA 461895a-f1.2

I like to play with dirt!

October 29, 2013

Guest post by Viviana Penuela

When people ask me what I do for a living, is very difficult to answer without getting into a philosophical debate on what biology is. That’s because I study biogeochemistry – which might mean nothing to the average person – but is basically the study of how chemicals produced in biological processes cycle through the geological matrix of an ecosystem. At the end it’s just a fancy way of saying we like to play with dirt. But we call it soil and we don’t just like it, we LOVE it. Now admit it, when was the last time you considered what goes on inside the “black box” called soil?  The organisms in soil, from microbes to macro fauna, and the chemical processes they drive, are literally the foundation of many of the ecosystems we as scientists study. After all, few people realize that soil color is driven in part by decomposition of leaf litter by microbes.

So how does biogeochemistry fit into my research? For the biological component, I study fungi. These misunderstood individuals – mostly because they are understudied – play a big role as decomposers, soil engineers, symbiotes to plants, and parasites (yes, there’s also some bad guys). Fungi influence the chemistry of the soil by breaking down complex chemical into smaller components, transporting nutrients to and from plants and by physically influencing the composition of soil.

Fungi and soil interaction

Fungi and soil interaction

I am interested in understanding this last mechanism and how it influences the ability of soils to store carbon and other nutrients. Fungi serve as temporary support that lets soil particles come together and form clumps, also known as aggregates. In the process of aggregate formation, organic matter is embedded inside the clumps. By this mechanism, organic matter is locked inside the soil clump and is not easily accessible for microorganisms to eat or decompose. This way, the soil prevents nutrients from escaping out of the systems as by-products of insatiable microorganism or by filtering out of the soil. At the same time it increases the health by increasing the amount of carbon and nutrients stored in the soil.

Fungi serving as temporary support for soil aggregates

Fungi serving as temporary support for soil aggregates

 

Because fertility of soils is a big part of agriculture, most of the studies on soil aggregation have focused on agricultural land. Newer farming methods, such as minimal overturning of the soil, have come about in part by the need to not disrupt soils. Keeping soil clumps intact retains nutrients for future crops. But have you ever wondered what happens underground on your own backyard? I have, and this is the question that drives my research. I want to know if there are aggregates in urban soils, and how well they store organic matter. Do city fungi work as hard as the country fungi? Is the way you water your lawn affecting the formation of soil clumps? Could we have a better grass “crop” in our yards if we change our lawn care practices? These questions from urban ecosystems are yet to be explored and the best tools we have are ecological principles that we can apply to very familiar environments, in this case our own backyards.

The “rice” no one wants to eat

October 23, 2013

Guest Post by Ashley Lackey

Working as a veterinary assistant, I am routinely exposed to what most people would consider disgusting situations.  Besides cleaning up fecal matter, and other bodily excretions on a daily basis, I get the chance to take samples of these different fluids and examine them for parasites. A parasite is an organism that lives in or on a host and acquires its nutrients at the expense of the host. Not all parasites make their hosts ill; the number of parasites in a host is often related to the level of severity of the infection.

A cat was brought in to the Pet Hospital, the owner was worried because she had been seeing small worms, she described as “the size of a grain of rice” coming out of her pets rear; the owner stated she would see these little grains of rice all around the house especially where the cat would take her naps.

Tapeworm segments seen around the anus

After speaking with the owner, the veterinarian recommended a fecal float examination. I took a sample of feces from the cat, and when I took a look under the microscope I found numerous tapeworms eggs (Figure 2).

Tapeworm ova seen in a fecal examination microscope slide

Figure 2. Tapeworm ova seen in a fecal examination microscope slide.

The cat owner was informed of the findings and was informed of the life cycle of the feline tapeworm (Figure 3). This life cycle involves an external parasite of the cat, a flea. Once attached to the cats intestine the worm begins to feed and reproduce. The veterinarian recommended Praziquantel (a drug used to expel flatworms from the host) and Revolution (a long term flea prevention to prevent the cat from being infected with this parasite in the future) for treatment of the infection.

Feline tapeworm life cycle

I became intrigued by Cestoda (the class of parasitic flatworms commonly called tapeworms). There have been over 1000 described species of tapeworms and virtually all vertebrates can become parasitized by at least one species of tapeworm.  Tapeworms are particularly interesting parasites because they display a variety of complicated life cycles with many intermediate hosts (also called transition hosts) to infect the definitive host (the host in which the parasite reaches complete maturity and can reproduce).

As I read more about tapeworms, I developed interest about the “crowding effect” in tapeworm infections. The “crowding effect” is when the number of worms in a host increases, the size of the individual worms decrease. In other words, a host with lots of tapeworms will have smaller worms than a host with few tapeworms. This can be caused by many reasons including competition between the worms and the role of the host’s immune system.

Currently, I am beginning a meta-analysis approach to research the “crowding effect” in tapeworm infections. Meta-analysis is a research method focused contrasting and combining results from different published studies in hopes to identify a significant pattern. I would like to find out if the “crowding effect” is seen in both cases where the host has tapeworms of the same species in the gut, and when different species of tapeworms reside in the host. Competition is expected to vary depending on whether the tapeworms are more or less related, and this should have an effect on the number and size of the worms. I hope to find out that the crowding effect is more prevalent in hosts that have many of the same species of tapeworms than different species. This research will lead to a better understanding of tapeworm infections in vertebrates and may even help us realize the value of the success of tapeworm treatment.

There’s a monster in my yard

October 22, 2013

Guest post from Jamie Gluvna

It’s 6:30 AM on a late-July morning. Mom and Dad are rushing around the house, grabbing their lunches and travel mugs of coffee, then leaving chore lists for my brother and me. I roll out of bed, dress, grab the notebook and a pen and head to the backyard. What was originally Dad’s idea of summer entertainment is now so fascinating that I don’t mind dragging myself out of bed when most other nine-year-olds are sleeping in.

I hike my leg over the hip-height black fence. There is a monster in this backyard—or at least, we hope there will be soon. Its leaves come up to my belly, and I push them aside to reach the nearest yellow-orange flower. I gently push back the petals, just like Dad taught me. This flower is a male. It has a simple flower structure in the center called an anther, and it’s covered in yellow dust—pollen. I swipe my paintbrush across the surface, filling the brush with pollen. I approach a female flower, which has a more complicated structure inside, and instead of powdery pollen, a clear liquid. The structure is the stigma, and the liquid is nectar. With the paintbrush, I dust as much pollen as possible onto the sticky stigma. I write down the date in my notebook under “Pollinations.” Next week, I’ll check to see if the area under the female blossom is growing larger, like a golf ball instead of a marble. I cross my fingers.

Next, I measure two beach ball-sized fruits on another vine and write down their sizes. Unlike the doorjamb in our kitchen marked with our heights over many years, this notebook holds just this summer’s measurements. One yellowy-beige fruit is growing very fast, and the other is growing steadily. I note this with a sigh, break off the faster-growing fruit, and toss it in the compost. If it grows too quickly, it will have thin walls and later it could burst. Leaving just one fruit per plant ensures there will be enough energy to grow a single, giant monster.

Fast-forward to October. Now, there is a monster in the backyard which can’t be missed. A giant pumpkin peeks out above the black fence. Six neighbors help us load it into our van, then we hit the road.

Later that night, we return with a cash prize and a plaque: “Ohio’s Largest Pumpkin, 1996.” The subtitle reads: “557.5 pounds.” Dad yells for me to go grab the small shovel and a saw. Now, we have a monster on our porch—the biggest jack-o-lantern anyone has ever seen. But, I also grew within myself another “monster”, a thriving interest in plant biology which has since fully shaped my career.

JG pumpkin

Epigenetics and Intelligent Design

October 9, 2013

Guest post from Marta Robertson

I study epigenetics, a field that has quickly become high profile among people who want to debate evolution. Epigenetics (literally meaning “above” genetics) refers to changes in traits not based on DNA sequence alone. These changes can be responsive to the environment, which helps us explain why individuals with the same genetic code, like twins, can grow to be different people during their lifetime. More specifically, I ask how epigenetic code can be inherited from parent to offspring, in much the same way as DNA. This means that a parent’s life experiences can affect their offspring; when a mother smokes, her children have an increased risk of asthma, and so do her grandchildren even if they never smoke. It’s awesome that everyone is as interested in epigenetic inheritance as I am, but unfortunately, sometimes epigenetics is misconstrued to support ideas that are not supported by science.

Marta_DirectExposure

            The really cool aspect of my research is that it is possible to have evolutionary change in a population without changes in DNA. This idea adds a new component to our general understanding of evolutionary change. It helps us explain how things change over time, and how big changes in traits can occur very quickly. Unfortunately for us, proponents of Intelligent Design (ID) think this outcome is pretty cool, too.

Intelligent Design is the idea that life on Earth is so complex, it could not exist without a “designer” or creator. Intelligent Design was the subject of the famous Kitzmiller v. Dover lawsuit, in which the school district in Dover, PA tried to include Intelligent Design in textbooks. The court saw Intelligent Design as disguised creationism and they lost. But some people still push Intelligent Design as an alternative to evolutionary theory, and they jump on the epigenetics bandwagon.

            Why? Because, as ID supporters say, epigenetics undermines evolution, or “Darwin’s theory,” by side-stepping DNA. But evolutionary change is not just changes in DNA. Sometimes DNA changes. Sometimes epigenetic code changes. Sometimes full traits change. It’s all part of evolution. Epigenetic code helps create variation in traits, some of which are better than others. Since that’s the same way we think about DNA changes, epigenetics isn’t really a big leap, and doesn’t come close to undermining evolution.

Recently, comments my advisor made in a news interview made their way on to uncommondescent.org, a popular Intelligent Design website. She said there is controversy about where epigenetic inheritance fits within the current understanding of evolution. However, on that website, people are using her comments as proof that evolution is not fact and “experts” are wrong. Of course, this is not what my advisor was saying, but it sounds good to anyone who wants to challenge evolutionary theory. I’m excited that so many people want to talk about epigenetics. But let’s talk about it accurately. Epigenetics isn’t mind over matter. Epigenetics doesn’t disprove evolution. Epigenetics is offering an increased understanding of cancer. Epigenetics is contributing to a better understanding of disease. And epigenetics is contributing to more robust agriculture. Let’s switch the focus to that!

We were there for the trees

October 2, 2013

Guest post by Carolyn Cheatham Rhodes

We were there for the trees.

It was supposed to be another day in the woods. Just one more hike to one more tenth acre plot to be sampled to better understand the forest in the Tampa Bay Watershed.  But this time, the rainy season was in full swing.  The Hillsborough River had swelled over its banks and spread out across the forest.

What should have been an uneventful trek through the woods was now turning in to a nerve-wracking slosh through dark, tannin-stained waters that were getting deeper with every step closer to our destination. Boot-deep quickly transitioned to knee–deep, then all too soon the water was lapping at our thighs. Hidden creek beds swallowed the shortest of our group up to the waist. Bolstering our resolve, we pressed on to our destination.  The adversity was making the task an adventure.

The GPS struggled to maintain its satellite connection beneath the thick cover of trees. Eventually, it led us to a spot we had previously measured during a very dry summer some years ago. This time most of our ~74 ft. diameter sampling area was under water save one spot, an island in a blackwater sea, on which stood a singular massive bald cypress.

credit Luisa Falck

credit Luisa Falck

The stately cypress towered over us as we splashed about, measuring the other trees in the drowned plot. Saving the massive tree for last, we completed our measurements and set off through the mire again to make our way home.

The data collected that day on the number and kinds of trees, their sizes and health were added to a growing database of forest samples through out the Tampa Bay Watershed. Researchers are using the data to better understand the forests of the Tampa Bay watershed, how the forest composition and health impacts the health of Tampa Bay, and to guide sustainable management decisions for the forest and the bay.

The field crew has moved on. Nine different scientists – all women – sampled over 700 plots (500 of them twice) across five counties in the Tampa Bay area over a span of five years. We are now professional foresters, graduate students, ecologists, wives, and mothers.  We look back on those days in the field and wax poetic about our trials and tribulations in the woods. We were never daunted. Whether it was muck and mire, dust and heat, or sweat and mosquitoes that awaited us at the end of the trail, we always marveled at the trees… we were there for the trees.

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