Archive for the ‘Local Research’ Category

Implanted Genome

Posted by amanda on Friday, May 21st, 2010

Mycoplasma

Mycoplasma

Is a rose still a rose if it doesn’t smell as sweet? Is a Mycoplasma capricolum still a Mycoplasma capricolum if it expresses a different genome? The answer to the first question is definitely “Yes” (especially if you could smell the roses I received on Mother’s Day). A paper published yesterday in Science confirms that the answer to the second question is a big fat “No”. Researchers at Maryland’s own J. Craig Venter Institute (JCVI) in Rockville in collaboration with their sister institute in San Diego are the first to successfully implant a new genome into a bacterial cell to create a new self-replicating bacteria that never existed before. In the most simplistic description, they created a unique new life.

Using a novel technique in which large DNA sequences were strung together in yeast, a 1.08 Mbp (Mega base pairs, where a base pair is one unit or nucleotide of double-stranded DNA) encoding all the necessary genes to make Mycoplasma mycoides JCVI-syn1.0 was synthesized. After synthesis, the circular chromosome was implanted into the nucleus of a similar species, Mycoplasma capricolum, for gene expression. This was not easy. After the first attempt failed, the researchers found a single mutation limiting proper gene expression. In their paper, the scientists recall several obstacles that had to be overcome: They needed to develop a method to extract large chromosomes from yeast, learn how to transplant these genomes into a recipient cell, and to choose a fast-growing recipient with the required gene expression machinery as a donor.

By synthesizing the DNA themselves, the researchers were able to include “markers” within the sequence. For example, if the genes were successfully expressed, the bacteria would be blue in color. Furthermore, they were able to leave a lasting mark on the DNA sequence by including strings of nucleotides (that when expressed into protein) spelled out an email address, the names of the scientists involved in the project, and a few famous quotations. [It isn't clear whether or not these proteins would actually be expressed. If only you could make an enzyme composed of a Shakespeare quote.]

This paper has raised some ethical and therefore political issues. President Obama has already asked the White House bioethics commission for a review of the issues to be provided to him in a report within 6 months, stating that the creation of a new genome raised “genuine concerns”. The application of this method for the synthesis of novel compounds using bacteria, such as biofuels, make this an important industrial topic as well. Can you patent an organism that you created? Would the laws that apply to genetically engineered crops where patents are in place apply to this as well?

In the last paragraph of the paper, the researchers write:

“We have been driving the ethical discussion concerning
synthetic life from the earliest stages of this work (25, 26). As
synthetic genomic applications expand, we anticipate that this
work will continue to raise philosophical issues that have
broad societal and ethical implications. We encourage the
continued discourse.”

Let the discourse begin.

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Hubble Hubbub

Posted by amanda on Wednesday, May 5th, 2010

Hubble movie

2D talk before the 3D movie

When you see a star-filled picture of space, chances are it was taken by the Hubble Space Telescope (HST). Last night, my daughter and I were treated to a screening of the Hubble 3D IMAX movie at the Maryland Science Center celebrating 20 years of the HST orbiting the earth.

Before the show, Dr. Jennifer Wiseman, NASA Goddard Chief of the Laboratory for Exoplanets and Stellar Astrophysics, gave a brief history of HST’s adventures in space. In 20 years, HST has orbited the earth over 110,000 times, viewing the universe in a way we never could with ground telescopes. Although it was launched on April 24, 1990, the pristine images that Hubble is known for weren’t possible until December of 1993, when a repair crew carried by the Space Shuttle Endeavor replaced faulty parts and updated others. Whether or not the astronaut crew would be able to complete the difficult repairs was unknown, and the repair was an anxious time for scientists at NASA Goddard who could only watch and hope from the ground. Due to the astronauts’ success at that and other maintenance visits to the telescope, we have garnered immense insights into the birth and death of stars, the distance of far-off galaxies, and the origins of the universe. Servicing Mission 4 in May of 2009 is expected to extend the life of the HST to at least 2013.

The IMAX movie itself centers around the first astronaut visit, and the joy of astronauts and researchers when the HST finally reaches its full operational potential. The repair portion of the movie is flanked by beautiful in-depth images of nebulae where you enter a star nursery and view what may be the origin of a new galaxy. Besides the drama of space and science, there is also humor, due mostly to astronaut Drew Feustel.

If you have any interest in space or just an interest in looking at beautiful pictures, see this movie. Viewing the achievements of scientists, astronauts, and the NASA program will inspire you. During the movie, my daughter kept reaching her hands out to catch the stars, certain that the universe was within her grasp.

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Oral Flora

Posted by amanda on Saturday, April 17th, 2010

mouth

Mouth with probably over 240 species of bacteria inside
http://www.flickr.com/photos/mbaruzza_2/

It’s been an interesting week in the stratosphere with a fireball in Wisconsin caught on video and a giant ash plume from the eruption of Iceland’s Eyjafjallajökull volcano.

But I’m feeling a bit introspective. Published in The ISME Journal, researchers (including a couple from the J. Craig Venter Institute in Rockville and the Institute For Genome Sciences at the University of Maryland School of Medicine) finally determined the bacterial diversity of our mouths or at least of 10 lucky individuals.

The researchers collected 26 separate samples from different parts of each healthy person’s mouth and pooled them, collecting and amplifying the RNA sequences present. RNA (or ribonucleic acid) contains the important coding information from DNA. RNA is necessary to every living organism, transcribed from DNA and translated into protein. Without RNA, there would just be pieces of DNA code, unable to be read or to be used as a template to construct protein. By isolating and amplifying a specific piece of RNA present only in bacteria, scientists are able to determine specific species through deciphering the sequences. In this study, around 1000 sequences per mouth were analyzed.

So what did they find? Contrary to past estimates that the mouth harbors 500-700 different bacterial species, this study found about 240 belonging to 9 different phyla or groups. As you may expect, not every mouth is the same. Subject 4 had the greatest number of bacteria (lucky duck), and only around 50 different species were expected to be shared between any two individuals with 11 shared between all 10 of the people studied. If you’re really into species (and who isn’t?), the magic 11 are: Haemophilus parainfluenzae, Streptococcus oralis, Streptococcus sanguinis, Granulicatella adiacens, Veillonella parvula, Veillonella dispar, Rothia aeria, Actinomyces naeslundii, Actinomyces odontolyticus, Prevotella melaninogenica and Capnocytophaga gingivalis. Interestingly, although every subject had sequences belonging to the group of bacteria known as Neisseria, no single specific Neisseria species was shared across all subjects. Our mouth bacterial flora also appears to be very distinct from that found in our colon, confirming that these are very different environments (as if we didn’t know that already).

It’s already known that bacterial flora can be passed from mother to child. I wonder if this study had been conducted with healthy couples who kiss frequently, if they would find a more similar bacterial diversity than 10 strangers. But that study probably isn’t a strong candidate for NIH funding.

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Star Light, Star Really, Really Bright

Posted by amanda on Friday, March 26th, 2010

hubblep3-300x300

NASA Hubble Space Telescope Collection

The universe is expanding, and from far, far away in space and time, astronomers can see the formation of massive galaxies. These bright clusters of stars more than a few million light years away appear redder (or redshifted) than closer stars which helps in determining their distance and thus, time, in the development of the universe. Astronomers study these distant massive galaxies to better understand the timescale of galaxy formation and how galaxy shapes are formed, such as disks and bulges.

Observation of some of these massive galaxies in the early Universe (known as sub-millimeter galaxies due to their wavelength, or high redshift) has revealed a very high rate of star formation, higher than expected from models. One hypothesis for this fast rate is the possibility of the merging of two gas-rich galaxies. Direct examination of the star-forming regions of these very distant galaxies has been difficult due to the limitations of modern-day telescopes.

In a paper published this week online in Nature, a group of scientists, including two from the Department of Astronomy at the University of Maryland, use a unique solution to study one of these massive galaxies from the young Universe. By studying a sub-millimeter galaxy (known as SMMJ2135-0102), they took advantage of strong gravitational lensing that magnifies the galaxy from the bending of light by massive galaxy clusters that lie behind them. With this magnification, they then used high-resolution sub-millimeter imaging to resolve the star-forming regions at a linear scale of only 100 parsecs (one parsec is about 3.26 light years or 31 trillion kilometers), only slightly higher than the resolution of viewing giant molecular clouds in our own Milky Way.

By comparing brightness and size between the high redshift galaxy and local galaxies and molecular clouds in the present-day Universe, the researchers found that the star forming region was not only 100 times larger, but also 100,000,000 times brighter. And although the star-forming energetics are much higher than local galaxies, the underlying physics of the processes are the same. Because the physics are similar, this means that techniques used for star-forming processes in the Milky Way can be used for sub-millimeter galaxies.

So physics has not changed between the early Universe and the present-day Universe — young Universe galaxies are just really, really big, bright, and productive.

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The Internal Compass

Posted by amanda on Thursday, March 11th, 2010

Billions of white blood cells are streaming through your bloodstream. They’re on patrol, defending you from foreign invaders and protecting you from infection. Some respond to parasites, others to viruses and allergens. When certain white bloods cells called neutrophils detect an infection or area of injury, they will move in, engulfing and digesting any foreign bacteria or fungi in their path. But how does a neutrophil know where to go? How does it sense its target? What is its internal compass?

Neutrophils, and many other cells, use chemotaxis, the detection and directed movement of cells in response to a chemical gradient. In an advance publication of the Annual Review of Biophysics, Kristen Swaney and members of the Devreotes Lab in the Department of Cell Biology at Johns Hopkins University review the process of chemotaxis in eukaryotic cells (like our neutrophils). Much of what we know about chemotaxis in these cells is from the study of Dictyostelium, a soil-living amoeba commonly (and lovingly?) known as slime mold.

YouTube Preview Image

Neutrophil chasing a bacterium

The process of chemotaxis does not actually begin with signal detection but with random cell movement. Cells like neutrophils and Dictyostelium extend pseudopodia (literally “fake feet”) made up of filaments consisting of many molecules of actin protein. The actin in these filaments interacts with myosin protein at the cell’s end, causing contraction (just like in your muscle cells), propelling the cell forward. After extension, the cell reassembles the actin filaments, so it can begin again. With this ambling gait, the cell moves in a random direction. In the absence of an attractant, cells extend pseudopodia from each side uniformly. But once the cell senses an attractant, pseudopodia extend toward the signal. Most notable is the wave-like motion through the cell when an attractant is present. This wave is caused from the recruitment of actin-binding proteins sequentially from the inside of the cell to points on the surface and may underlie the generation of pseudopodia.

Cells detect chemical attractants with receptors on their surfaces. Once receptors bind an attractant molecule, a signal cascade is initiated and a network of signaling pathways is activated leading to the formation of actin into filaments and movement. Eukaryotic cells are capable of sensing both the amount of attractant and the location of the attractant in space, detecting how many receptors have bound attractant and where those receptors are located on their surface. Interestingly, if an attractant is present in low amounts, the cell will “adapt” to the presence of attractant and actually be more sensitive to an attractant gradient by ignoring the background.

Genetic analysis of Dictyostelium has revealed a complex and wide range of interacting players in the process of chemotaxis. In her review, Swaney emphasizes that we still have much to learn about the components involved in wave propagation, the mechanism of attractant adaptation, the localization of components, and the complexity of multiple signaling networks. There are many pieces to an internal compass.

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Regression in the Dark

Posted by amanda on Friday, March 5th, 2010

Why don’t humans have tails or gills? Why aren’t we covered in hair? Why don’t we have all the traits of our primitive ancestors? When we think of the advance of evolution, we may think of increasing complexity, but many traits are lost due to regressive evolution. Regressive evolution is the disappearance of an ancestral trait or characteristic over time.

Surface FishCavefish

A. mexicanus Surface Fish and Cavefish; Courtesy of William Jeffery

In order to better understand how regressive evolution occurs, scientists have found a model organism among cave-dwelling animals. Cavefish, like most cave-dwelling animals, have lost their eyes and pigmentation over time. And interestingly, they can interbreed with their surface-dwelling counterparts who still have eyes and normal pigment, making them a model tool for understanding the genetics of trait loss.

How are traits lost in evolution? It may be that genes responsible for these traits are mutated or lost due to their lack of advantage. Or perhaps it is somehow more beneficial to not have the lost trait due to energy conservation. A third theory is that lost traits may be negatively linked to other traits that now benefit the organism in a new environment. When one gene affects many traits, this is known as pleiotropy.

In a recent review in the journal Annual Review of Genetics, William Jeffery, a professor at the University of Maryland’s Department of Biology, discusses regressive evolution in the cavefish Astyanax mexicanus. Known as the Blind Tetra, A. mexicanus is native to 30 known caves in Mexico but can now be found in laboratories around the United States due to its short reproduction time, simple diet, and frequent spawning. Although cavefish appear eyeless, they actually have small nonfunctional eyes in a smaller eye socket completely covered with skin. In Jeffery’s lab, when a cavefish embryo is transplanted with a surface fish lens, the cavefish is able to develop an eye, containing a retina lacking pigment. The lens of the eye prevents cell death in the retina. Because the surface fish lens was able to rescue eye development, this suggests that the lens has a fundamental role in regulating eye degeneration and may be the crucial trait that is lost in the regressive evolution of eyesight.

From genetic studies, it is estimated that up to twelve separate genes are responsible for eye loss. One of these genes (known as shh), affects both eye degeneration and the enhancement of oral and taste bud development, traits that would be advantageous to a cave-dwelling fish. This indicates that pleiotropy may play a role in eye regressive evolution. Jeffery stresses that more than one of the three possible theories for regressive evolution may be responsible for eye loss in cavefish. The search to identify all of the genes that affect eye degeneration in A. mexicanus is underway and may lead to insights about our own regressive evolution.

I wish I could trade in my spleen for a tail…

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Henrietta Lacks

Posted by amanda on Tuesday, March 2nd, 2010

March is National Women’s History Month. In celebration, I plan to make one post a week featuring women that contributed significantly to science in Baltimore.

Immortal Life of Henrietta Lacks

I want to start with Henrietta Lacks, a woman from Turner Station whose cancerous cells were taken and turned into one of the most powerful scientific tools we have today. The tumorous cells that were removed from Henrietta’s cervix at Johns Hopkins Hospital during her treatment in 1951 were the first immortal human tissue cells to be cultured. First grown in the lab of George and Margaret Gey, Henrietta’s cells can be maintained indefinitely and have been used for countless experiments to study everything from cancer to the effects of atomic radiation on human tissue. Named HeLa, these cells led to advances in human genetics, such as the numbering of chromosomes, as well as to the cell culture, cloning, and in vitro fertilization methods we use today.

The Immortal Life of Henrietta Lacks by Rebecca Skloot is an excellent read on the history of Henrietta and HeLa cells and highlights the moral and legal dilemmas of tissue collection. In her book, Skloot discusses how the Lacks family (who still reside in Baltimore) did not know about the use of HeLa cells until decades after their spread into laboratories around the world, and that while biotechnology companies that produce and sell HeLa continue to profit, the Lacks family has struggled with affording health insurance.

According to Skloot, there has never been an official effort by Johns Hopkins to honor Henrietta Lacks and her biological contribution to science. With the amazing press Skloot’s book has generated, I have a feeling this may change soon.

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Nano Nano

Posted by amanda on Thursday, February 25th, 2010

Carbon Nanotube

Carbon Nanotube; http://www.flickr.com/photos/ghutchis/ / CC BY-ND 2.0

Imagine a tiny tube. Now imagine it even tinier than that — so tiny that not even a single molecule of caffeine can pass through it. Carbon nanotubes, some only fractions of a nanometer (one billionth of a meter) in diameter, consist of seamless graphite layers shaped in cylinders with one capped end that can extend several centimeters.

Discovered accidentally in 1991 by Sumio Iijima, carbon nanotubes, despite their small size, have the strongest tensile strength of any known material. Their extremely high thermal conductivity, electrical superconductivity, precise positioning of atoms, light weight, and potential for molecular transport provide numerous applications in electronics, aerospace, and medicine. They may even be used for the construction of space elevators, providing material for the cable to move things between Earth and space. (Not humans, though, unless we do something about that nasty space radiation.) In the US, the potential of carbon nanotubes was recognized in 2001 with the establishment of the National Nanotechnology Initiative program.

Carbon nanotubes can have single or multiple walls. Single walled tubes have higher thermal conductivity and more desirable electrical properties for use in electronics and heat transport. Multiwalled tubes have potential as biosensors in medicine and laboratory science used to detect microscopic amounts of chemical or biological compounds. Nanotubes have potential in drug delivery and targeted treatment, although studies have shown nanotubes to be toxic in mice if they reach the lungs.

Unruly Mass of Nanotubes

NASA Goddard Photostream; Image credit: Yuki Kimura, Tohoku University

With the immense interest in carbon nanotubes, a revolution of sorts in industry has occurred. The synthesis of carbon nanotubes generally requires the use of a cobalt or nickel catalyst. But most recently, Joseph Nuth of NASA Goddard in Greenbelt and colleagues described a new form of nanotube synthesis in Astrophysical Journal Letters that results from the recycling of carbon in space when supernovas explode. Instead of requiring a metal catalyst, a mass of nanotubes were produced when graphite dust particles were exposed to a mixture of carbon monoxide and hydrogen gases (using a known method for making  liquid fuel from coal). This research was spawned by the discovery of graphite whiskers, large carbon nanotubes, that were found associated with meteorites. If this new form of synthesis can result in lightweight and orderly tubes, it may mean an innovation for the nanotube industry.

In addition, the formation of these large nanotubes may be the reason supernovas appear dimmer than we expect from their distance alone. Imagine that: A nanotube-haze in space.

Read an article in the Baltimore Sun on Nanotechnology here.

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How do we taste?

Posted by amanda on Monday, February 22nd, 2010

What tastes good to you right now? A sweet carrot? A bitter beer? Or maybe some salty pretzels? Whatever it is, how it tastes to you is determined by your cells. So how do we taste?

boy eating cookies

We separate tastes for humans (and probably most mammals) into five categories: bitter, sour, sweet, salty, and umami (the taste generated when you consume certain amino acids, such as MSG). Our taste preferences when we are born are genetically encoded. We prefer sweet tastes as babies, because “sweet” is associated with healthy foods that contain proteins and energy. We avoid bitter and sour things, because these are associated with toxins and acidic foods, like spoiled fruits or harmful plants. Humans (and mice) generally prefer salty foods when our bodies are low in sodium with our tastes fitting our physiological need. As we mature (or most of us anyway), we acquire tastes for more bitter and sour things, such as coffee and lemons, and may prefer salty and sweet foods even though we really don’t need to build up our salt or sugar supply.

From studies in mice, it is thought that the five tastes are determined by separate taste-receptor cells (TRCs) in the mouth each tuned to a specific taste. TRCs are organized into taste buds, composed of 50-100 cells, and these taste buds are housed within papillae (the bumps on your tongue). Taste buds from all regions of the mouth contain cells that respond to the five tastes and are connected to nerves that carry taste information to your brain stem and into the primary gustatory cortex (where your response to a food and your perception of flavor is dictated). Contrary to popular belief, there is no “taste map” on the tongue.

Recently published online in Nature, Jayaram Chandrashekar and colleagues (including scientists from the National Institute of Health in Bethesda) illustrate how salty taste occurs in sodium sensing in mice. Each TRC that determines a salty taste contains a sodium channel (or sodium transporter). This channel is present in many cells within your body, including your kidneys, lungs, and sweat glands, and is important in salt transport. Its role is so important that if this channel is made completely nonfunctional in mice, death occurs soon after birth. In order to study the importance of this channel in taste, scientists used a clever technique (attaching the channel mutation-causing agent to a known TRC-specific gene) to generate mice that were missing the sodium channel only in their taste buds. Unlike their ‘normal’ peers, these mice displayed a complete loss of salt attraction and sodium taste response while responding normally to the other four tastes. And most importantly, all of the TRC cells that carried the mutated salt channel did not carry any markers for the other four taste sensors, showing again that individual TRC cells are only able to determine one taste.

Whether or not this specific sodium channel is as important to salty tastes in humans as it is in mice is unknown. Due to our molecular similarities, the authors note that it is likely. But unlike mice, our innate responses to salty taste may be overridden by our high-salt diets.

Now, pass me those fries. All this talk of salt has made me hungry.

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The Genetics of Stuttering

Posted by amanda on Thursday, February 18th, 2010

When we think of genetically affected characteristics, we often think of hair and eye color, height, and the size of our nose. But what about speech? This week, Changsoo Kang and Dennis Drayna, from the National Institute on Deafness and Other Communication Disorders in Bethesda, and colleagues report on the genetics of stuttering in the New England Journal of Medicine.

Stuttering is found in all cultures and languages, affecting 5% of children in twice as many boys as girls. Nearly 80% of childhood stuttering resolves itself, mostly in girls, leaving male stutterers outnumbering female stutterers 4:1. 60 million people in the world are stutterers, and Winston Churchill, John Updike, King George VI and James Earl Jones join their ranks. The history of stuttering is fraught with erroneous theories and damaging medical practices. The ancient Greeks thought that stuttering resulted from tongue dryness and recommended enlargement of the veins by surgical or chemical means. In the 1800s, stuttering was thought to be an anatomical defect, and surgical treatments were popular. By the 1900s, stuttering was ruled a psychological disorder and treated with conditioning and psychoanalysis that were eventually proven ineffective. The modern theory is that stutterers have a neurophysical problem that disrupts the precise timing in speech.

human chromosomes

Human chromosomes; NIH

The evidence for a genetic component to stuttering is apparent, such as the existence of identical twin stutterers and a high incidence of stuttering in first degree relatives. Approximately half of stutterers have a family history of the disorder. By examining genetic linkage in families of stutterers, geneticists have honed in on several chromosomes that may be involved in stuttering.

recycling

In Kang and Drayna’s most recent study, they’ve focused on chromosome 12 to examine the genes involved in stuttering in the largest well-studied group of stutterers, a Pakastani family simply known as PKST72. By comparing the DNA of stutterers in the family to non-stuttering control subjects, the researchers were able to pinpoint the genetic sequences affected in stuttering individuals. Interestingly, the genes they identified affect the cell’s recycling center, the lysosome. The lysosome takes unwanted material in the cell, such as old proteins, and breaks them down into something more usable. In this family of stutterers, the genes that direct proteins to the lysosome for recycling are mutated, most likely resulting in a build-up of this cell litter in other compartments of the cell. Somehow this accumulation of trash in cells leads to speech disturbance. The way this occurs is unknown, and the implication of these results for both treatment of stuttering and future studies is profound.

One other thing of note is that all but two of the stutterers with these mutations were heterozygous, meaning that the mutations were only found on one of the two strands of chromosome 12. If the mutations were found on both strands of DNA, the affected persons may have had a severe lysosomal storage disease called mucolipidosis.

DNA is amazing.

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