Category: Genetics/Genomics Page 10 of 11

Varmus Encourages Provocative Questions

On April 16, 2012

In Biology, Cancer, Genetics/Genomics, Global Health, Lecture, Medicine

By Nonie Arora

“Provocative questions,” the important but non-obvious ones, the questions to be answered by technology that doesn’t exist yet, are one focus of Nobel Laureate Harold Varmus‘s storied career these days.

What environment factors change the risk of various cancers when people move from one geographic area to another?

Why are different tissues so dramatically different in their tendency to develop cancer?

How does obesity contribute to cancer risk?

Harold Varmus, Director of NCI Source: cancer.gov

Varmus, director of the National Cancer Institute, visited Duke April 12 to address the Duke Medical Scientist Training Program 2012 Symposium and to share some of these provocative questions with a full house in Love Auditorium.

Varmus said we are in a period of rapid scientific change because “clinical research and basic research are mingled in a way that is extraordinary.” And while he acknowledged recently flat NIH budgets, he said, “let’s not worry about budgets, let’s worry about opportunities.”

For example, he cited one such scientist who looked for important opportunities, Renato Dulbecco (1914-2012), a virologist from Caltech who died recently. Dulbecco advocated for a systematic approach to sequencing the human genome as early as 1986 despite the many naysayers in the biology community. Varmus called Dulbecco, “a visionary who saw beyond the technology of the day” as he encouraged his audience to think in the spirit of Dulbecco: boldly.

Varmus spoke of how the “precision medicine” of genomics may lead to more accurate diagnoses and a new taxonomy of disease. He made the distinction clear between precision medicine and personalized medicine claiming that even his father practiced personalized medicine because he knew his patients well.

Cancer deaths are rising globally, especially in less developed countries, according to Varmus. He explained how open exchange of information with cancer centers around the world is important to solving new cancer challenges. He described how cancers are more frequently related to infectious agents in the developing world, like the Epstein-Barr virus’s relationship to Burkett’s lymphoma, and the implications for research.

To fund important but non-obvious questions in cancer research, he has launched the “Provocative Questions” Project. These questions are meant to build on specific advances and address broad issues. Because researchers can be more risk-averse when funding levels are lower, this project hopes to fund intriguing questions that would otherwise remain unfunded and unanswered.

These questions need answers. Who better to answer them than the Duke MD/PhD candidates in the audience.

Raiders of the Lost Blood Spots

By sa160@duke.edu

On March 2, 2012

In Genetics/Genomics, Medicine

By Nonie Arora

Blood Spots Assessed by CDC

Almost every newborn in the United States is pricked on the heel within hours of birth for a few drops of blood that are then tested for conditions like PKU, sickle cell anemia, and cystic fibrosis. But then the sample is often put on small piece of blotter paper and filed away by the state. Few parents know about these millions of residual dried blood spots.

Alex Kemper, Duke professor of pediatrics and community and family medicine, spoke at the Genomics and Personalized Medicine Forum on the “raiders” of these lost blood spots, researchers who might use them to improve public health. Along with issues of science, he addressed the negative public reaction to research using stored blood spots. “Why does the government have my DNA?”

Dried blood spots have many uses beyond early detection of diseases. They can be used to improve quality of current screening tests and new screening approaches. In a few cases, dried blood spots have been valuable in forensic analysis to identify an abducted child. In this era of increasingly personalized medicine, being able to use blood spots for genomic analysis would provide answers to new research questions, Kemper said.

However, the differences in the way blood spots are stored present research challenges. Kemper is very interested in how environmental toxins affect children’s health. When his research team attempted to use dried blood spots to study how flame-retardants affect thyroid problems, they ran into a major problem. Because blood spots are often stored in an environment more like the warehouse from Raiders of the Lost Ark than a controlled lab environment, the specimens were too contaminated to use for research.

Besides the inherent quality concerns, the public is wary of researchers using blood spots because of the lack of consent and confidentiality. (See “Texas Newborn Bloodspot Saga”) Should researchers be able to use blood spots from infants without consent from parents? Should the blood spots be anonymized to protect privacy even though anonymization limits the types of research that can be performed?

These questions do not have easy answers.

States differ on legislation about the retention, confidentiality, and parental control of blood spots. Some states have no rules at all. Kemper claimed that many of these laws are currently in “a state of flux” because of pending lawsuits and changing public perceptions. As the rules change, one thing is almost certain: improving the genetic literacy of the public is essential to advancing uses of dried blood spots.

New Blogger Nonie: Joining the Team

By sa160@duke.edu

On March 1, 2012

In Cardiology, Genetics/Genomics, Students

By Nonie Arora

Hello there,

This is Nonie Arora, a freshman A.B. Duke Scholar from Novi, MI. I am excited to join the Duke Research Blog team.

I’ve been involved in research since my freshman year of high school. Back then, I was obsessed with the concept of “superbugs” and antibacterial resistance. I ordered E. coli out of a catalog with my chemistry teacher and tested its resistance to common household substances, like soap and bleach. My research interests evolved as I started working in a lab at the Wayne State University Medical School. For three years, I studied genes in a yeast, C. albicans, that contribute to antifungal drug resistance.

My research took me to different science fairs, such as the International Science & Engineering Fair (ISEF) and the Intel Science Talent Search. At ISEF, being in a hall with 1500 other students from around the world – who were all enthusiastic about research – was incredibly motivating. I was eager for more research exposure. The wide variety of research present at Duke, from basic science to behavioral economics to clinical trials, is incredible. Being able to interact with renowned faculty as a freshman is a privilege.

Last semester, I was part of the Genomics FOCUS program and took classes with Hunt Willard and Bob Cook-Deegan. The captivating teaching styles of my professors coupled with a better understanding of how science affects society increased my passion for genomics. This semester, I am working in the Kontos lab studying protein interactions that may explain how endothelial cells maintain a resting state, which is relevant to cardiovascular disease.

Outside of research, I like to run, read the New York Times, and devour law thrillers. When I have the time, I indulge in watching The Big Bang Theory, House, and the Good Wife. At home, I enjoy spending time with my parents and my 11-year old sister. It’s probably easier to answer some of the questions that my professors propose than the ones she does!

I look forward to contributing my perspective on research at Duke.

Max Leung, Caped Crusader Against DNA Damage

By Becca Bayham

On February 2, 2012

In Biology, Chemistry, Environment/Sustainability, Genetics/Genomics, Lecture, Students

By Becca Bayham

His lab colleagues call him Batman, the Toxic Knight.

To the rest of the world, he is Maxwell Leung, a PhD candidate in Duke’s environmental toxicology program. For the past five years, Leung has worked in the lab of Joel Meyer (AKA “Super-enviro-man”) fighting for environmental justice with pipettes and PCR machines.

Leung spoke about his research Jan. 27 as part of the Nicholas School’s continuing series on toxicology. Leung studies how exposure to certain environmental chemicals can affect organisms’ later-life development by damaging their DNA.

Cells contain two types of DNA: nuclear DNA (found in the nucleus) and mitochondrial DNA (found in mitochondria, which generate most of a cell’s energy).

“When people talk about DNA damage, they are usually referring to DNA damage and revision occurring in nuclear DNA,” Leung said.

A ligase enzyme repairs damage to nuclear DNA (National Institute of General Medical Science)

For the most part, special packaging and multiple repair mechanisms protect nuclear DNA from harm. However, mitochondrial DNA lack certain repair mechanisms, and little is known about their packaging. In the lab, Leung evaluated damage to both types of DNA by exposing worm larvae to short bursts of UV radiation. He found that, while nuclear DNA damage was partially repaired during the 24 hours between exposures, mitochondrial DNA damage continued to accumulate.

Further study of the exposed worms suggested that mitochondrial DNA damage at an early life stage can cause adverse effects such as reduced energy production, DNA transcription and oxygen consumption in adults. Given this connection, Leung sought to identify environmental chemicals that are capable of damaging mitochondrial DNA. Of the six chemicals he tested, one targeted mitochondrial DNA over nuclear DNA, and caused visible neurological effects: paraquat, a widely-used herbicide.

Which raises the question: if one out of six tested chemicals had this effect, then how many other environmental chemicals could cause that type of damage?

Unfortunately, mitochondrial DNA damage disproportionately affects neurological tissues; neurons require a great deal of energy and thus contain large amounts of energy-producing mitochondria. Studies have found strong associations between genes in mitochondrial DNA and neurodegenerative disorders such as Parkinson’s disease.

After the lecture, I spoke to Leung about why he decided to study science, and how he came to Duke.

“When I was in junior high, there was a TV show called ‘Success Stories’ in Hong Kong, featuring a number of famous Chinese scientists pursuing scientific careers in U.S. They went on to become National Academy members, win Nobel Prizes, and make important contributions to science and our world. That left an impression on me.”

Now, Leung hopes to write his own success story. He received his undergraduate degree in Food and Nutritional Science from the University of Hong Kong, and a master’s degree in Food Toxicology from the University of Guelph in Canada.

Leung came to Duke in 2007, following a visit to Joel Meyer’s newly-established environmental toxicology lab. At the time, the lab was “literally empty,” with just four PCR machines and a lab technician from Canada. Fifteen researchers work in the lab now, and each has been christened with their own superhero nickname including such characters as “Terror Byte,” the “Nano Ninja,” and “Wonder Worm Woman”.

“I enjoy the people I come across in science more than the science itself,” Leung said. “I enjoy doing experiments, giving talks and writing papers, but it is always the interesting people that I get to know through these activities that keep me going everyday.”

Sharing is caring, when it comes to scientific data

By Becca Bayham

On November 22, 2011

In Animals, Biology, Genetics/Genomics, Lecture, Medicine, Science Communication & Education

By Becca Bayham

Worms don’t typically evoke a sense of awe. But C. elegans nematode worms — all 558 cells of them — played an important role in how scientific data is shared today.

Scientists Robert Waterston and Sir John Sulston described this connection during the James B. Wyngaarden Distinguished Lecture on Nov. 14, sponsored by the Institute for Genome Sciences and Policy. [Watch the whole lecture – 1 hour, 9 minutes)

During the 80s, Waterston and Sulston were unraveling the nematode genome at their University of Cambridge lab. Worms make good subjects for study because they are finite, transparent and genetically manipulatable.

When Waterston moved from Cambridge to Washington University in St. Louis, he felt isolated from the research community he’d left. However, an informal and creatively-covered publication — the Worm Breeder’s Gazette (see photo at left) — helped bridge that physical divide. Researchers used the Gazette to share short summaries of their discoveries.

“Through this very informal means, the community was made aware of what was going on, and invited to share in it,” Waterston said. “Indeed, it worked spectacularly. Now we knew not just these anonymous pieces of DNA, but where they belonged. And that made [the data] much more useful for us and the community.”

Waterston and Sulston were the first to sequence a multi-cellular organism’s genome. Following their success with worms, the two moved on to the holy grail of science at the time: the human genome.

In terms of data sharing, “human genetics was the polar opposite of the worm field. Human geneticists held things very close to their chests,” Waterston said.

In 1996, the two scientists joined other researchers at a conference in Bermuda to discuss how human genome data should be handled. Should it be stored in proprietary databases, with limited access? Or shared freely with the world? Waterston and Sulston advocated for the latter, and this opinion ultimately prevailed. If it hadn’t, the humane genome story might have ended differently — or not at all. Data sharing “kept the lines of communication open” between researchers, Waterston said, and greatly facilitated the sequencing process.

Sure enough, following the human genome’s completion in 2000, the entire sequence was released into the public domain. Public data sharing has become standard practice for other animal genomes and other areas of science. However, even though Waterston and Sulston’s efforts encouraged data sharing on a massive scale, the tendency towards secrecy still exists.

“Pushing for more open science continues to be important,” Waterston said. “The nature of science is that private initiatives continue to push on public domain. If we don’t push back, we’re going to be the poorer for it.”

A sip or quick dip could change your DNA

By Ashley Yeager

On November 15, 2011

In Animals, Biology, Cancer, Chemistry, Environment/Sustainability, Genetics/Genomics, Global Health, Lecture

By Ashley Yeager

Micronuclei in mammalian cells form when DNA undergoes stress and not all the material makes it into the two new nuclei of a dividing cell. Credit: CRIOS.

As a long-time swimmer, I was a bit disturbed when EPA scientist David DeMarini said he had scientific evidence showing that extra time in the water could damage my DNA or even raise my risk for bladder cancer.

The damage, he said, comes from leftover chemicals from the treatment process in which bromine and chlorine are used to kill E. coli and other bacteria in drinking, bath and swimming water.

There are at least 600 of these chemicals, called disinfection byproducts or DPBs, released into the water after treatment, and DeMarini has spent more than a decade identifying them and how they interact with the molecules in our bodies.

Through his research, he has shown that many of the DPBs, whether ingested, inhaled or absorbed through our skin, can change our DNA. Yet, only 11 DPBs, all from drinking water, are regulated in the U.S., and none are regulated in any of the other developed countries, DeMarini said during a Nov. 11 Integrated Toxicology & Environmental Health seminar at Duke.

No one really thought about pool water until about five years ago because “people always thought swimmers weren’t at risk for anything. They thought, ‘swimmers are healthy, so why waste our time studying them,’ ” DeMarini said.

That assumption changed in 2007. Researchers in Spain found, based on interviews, that swimmers had a 1.6-fold increase for bladder cancer. Then, in 2010, DeMarini and his colleagues showed that after a 40-minute workout, swimmers’ cells created micronuclei, suggesting damage was done to the DNA so that another nuclei formed as the cell began to divide.

Together, the teams were able to identify a specific gene that makes some individuals more susceptible to DNA damage from DPBs, further increasing their cancer risks. About 28 percent individuals in the U.S. have this gene.

That doesn’t mean we should stop swimming, bathing or drinking municipal water though, DeMarini stressed. He said that the known benefits of drinking, bathing with or swimming in chlorinated water are still much greater than the potential health risks from DPBs.

“You’re naïve, though, if you think that the environment you live in is pristine,” he said. “It’s not.”

But to keep pools a little cleaner and reduce the burden of disinfection byproducts, he suggested not peeing in the water and showering before taking a dip. Drinking pool water is not a good idea either.

The 'Pre-research' Path

By Pranali Dalvi

On November 2, 2011

In Biology, Chemistry, Genetics/Genomics, Science Communication & Education, Students

By Pranali Dalvi

Senior Arun Sharma may be studying biology, chemistry, and genome sciences and policy at Duke, but don’t expect to see him trading in his lab coat for a white coat anytime soon. Sharma says he is ‘pre-research’ rather than ‘pre-med’.

His interest in research was piqued by his father, a physicist. Growing up in that lab-coat environment showed Sharma that he could one day make his own discoveries. After coming to Duke, Sharma realized he could start on this path early and immersed himself into research as a first-semester freshman.

“I thought it was cool that as just an undergraduate, an eighteen year-old, I was able to make new discoveries and participate in long-term research projects,” Sharma says.

Through the Howard Hughes Research Fellows Program, Sharma was matched up with his current mentor, Dr. Gerard Blobe in the Department of Pharmacology and Cancer Biology, where he has been investigating the molecular mechanisms behind angiogenesis, or blood vessel formation, in tumors. The concept behind his research is simple: if you can cut off the blood supply to the tumor, you can essentially kill the tumor.

Specifically, Sharma’s work revolves around the endoglin protein, a cell surface receptor in endothelial cells, which line the interior of blood vessels. Endoglin has a unique interaction with two other proteins (SMAD2 and BMP), which had not been previously characterized. When a specific member of the Bone Morphogenetic Protein (BMP) family binds to endoglin, SMAD2 is involved in a signaling cascade: SMAD2 is driven to the nucleus, where it prevents cell proliferation, or cell growth, and thus prevents angiogenesis. The long-term application of Sharma’s research would be drug discovery to initiate this signaling cascade and prevent angiogenesis, subsequently killing the tumor by cutting off blood supply.

Sharma wanted to share his passion for research with other undergraduates so he co-founded the Duke Undergraduate Research Society (DURS) along with classmates Peter Dong, Nick Schwartz, and Vivek Subramanian to show students that research is a realistic goal and that it is highly accessible to undergraduates.

“People think that in research you have to have a lot of training, a lot of background to get anything done productively,” Sharma says.

To encourage students to experiment with research (no pun intended!), DURS hosts renowned faculty speakers such as Dean Nancy Andrews from the School of Medicine and Steve Nowicki at lunch and dinner events. DURS– along with the Undergraduate Research Support Office – has also established Visible Thinking, an undergraduate research symposium – the largest of its kind – that gives students the opportunity to discuss their research with peers and faculty members during a poster session.

“I like to think that [this organization] is going to be my legacy at Duke after I graduate,” says Sharma.

After graduation, Sharma plans to attend graduate school to explore cardiovascular disease development and to eventually become a principal investigator (PI), leading his own lab.

“One thing I’m definitely going to do as a PI is something my own PI, Dr. Blobe, did: provide undergraduates with the opportunity to work in a lab,” he says.

Going DEEP in the Genome

By Karl Bates

On October 26, 2011

In Animals, Biology, Genetics/Genomics, Medicine

By Karl Leif Bates

Duke has a growing number of researchers looking into how genes are played differently from one organism to the next, based not on the spelling of their genes, but on cues their mothers gave them. The field is called epigenetics – epi meaning above or beyond the genes.

Same genes, different maternal diets. Amazing, huh?

Your momma (and probably daddy) clamped some of these external molecules called “methyl groups” onto your DNA, based on the environmental conditions they were experiencing. Methyl groups are a way of turning down a gene’s activity without changing its spelling or taking it out. It’s a neat trick, but it creates a huge new layer of complexity above and beyond just the bare-bones spelling of your genome.

In a landmark 2003 epigenetics study Duke’s Randy Jirtle showed that the color and size of second-generation mice could be altered simply by changing their mother’s diets. Their genes were essentially the same as their pale, fat cousins, but their mothers had clamped epigenetic controls on their DNA that made them darker and skinnier. (see Jirtle on Duke’s Office Hours)

A Wednesday morning symposium kicked off the existence of DEEP, the Duke Epigenetics and Epigenomics Program and introduced more than 140 members of the campus community to some of our leading researchers in epigenomics, the broad-based search for epigenetic changes.

I missed the first half of the show, but caught Susan Murphy of Ob-Gyn talking about a huge epigenetic study she’s doing with 2000 human mother-baby pairs right now. They’re hoping to correlate environmental factors during the pregnancy – nutrition, stress, smoking, alcohol etc. – with epigenetic differences in the babies from birth to age 5. And then, hopefully, they’ll find some insights into developmental differences, obesity, ADHD, diabetes, asthma, autism, etc.

Murphy said there are already some diseases thought to stem from epigenetic imprinting, and she’d like to find more. (Yes, it’s always a bad idea to smoke during pregnancy, and she already has the low-birth-weight data to prove it.)

Greg Crawford of Pediatrics and IGSP finished the session with a view of the huge landscape to be explored. Only 2 percent of human DNA is genes that make proteins. In their search so far for other areas of DNA that may be sensitive to signaling (as from epigenetic changes), they’ve found that maybe 12 percent of the genome is involved in sending and receiving signals. That still leaves 86 percent mystery.

Us vs. Them

By Prachiti Dalvi

On October 15, 2011

In Biology, Genetics/Genomics, Lecture, Medicine

By Prachiti Dalvi

Bacteria occupied Earth long before the evolution of humans. Inhabiting a wide array of environments and exhibiting unparalleled genetic diversity, bacteria share a unique relationship with humans. Some of these microscopic organisms are essential to life while others threaten our very existence.

Sir Richard Roberts, a 1993 Nobel Laureate in Physiology or Medicine and a Fellow of the Royal Society, spoke about the importance of bacteria to the world of science on Thursday in an event co-sponsored by the Duke Institute for Genome Sciences and Policy (IGSP) and Quintiles, a clinical research organization.

Roberts articulated the importance of understanding the structure of macromolecules in order to understand their precise function: a principle he has used to build his own career. The molecular biologist was awarded a Nobel for his discovery of introns in eukaryotic DNA as well as for explaining the mechanism of gene-splicing.

According to Roberts, although bacteria are generally looked at in a negative light, most bacteria are harmless. He expressed concern about the indiscriminate use of antibiotics. For example, the strength of the farm lobby has prevented the strict regulation of antibiotics administered to animals in the food industry. Here, antibiotics are being used to make animals weightier rather than to fight an infection.

Misuse of antibiotics can help bacteria generate resistance, making fighting these microorganisms in the future more difficult. In fact, when we develop an antibiotic we are simply “selecting for the next drug-resistant bacteria, and we are polluting ourselves out of existence.”

“We tend to lose track of just how interesting bacteria are,” says Roberts. “There was a time when an awful lot of NIH funding was set aside exclusively for bacterial research.” However, now, NIH funding is focused primarily on eukaryotic organisms despite the indispensible role bacteria play.

Science Under the Stars

By Karl Bates

On October 6, 2011

In Behavior/Psychology, Biology, Cancer, Chemistry, Climate/Global Change, Computers/Technology, Engineering, Environment/Sustainability, Genetics/Genomics, Physics, Science Communication & Education, Students

Building on earlier successes with K-12 classroom outreach and a huge appearance at the 2010 USA Science and Engineering Festival, Duke University students and faculty are inviting Triangle-area families to join them for an evening of interactive science demonstrations called SCIENCE UNDER THE STARS.

Duke students wowed kids and grownups alike at last year's national science festival in Washington DC.

The October 19 festival will include hands-on, all-ages activities from Chemistry, Physics, Biology, Engineering, Genomics, Environmental Science, Microbiology, Immunology, and Molecular Genetics.

SCIENCE UNDER THE STARS will be from 6 p.m. to 8 p.m. on Wednesday, Oct. 19, on the front lawn of the French Family Science Center on Duke’s West Campus.

At 7:30, the chemists will stage a spectacular grand finale — not quite fireworks, but close!

Free parking is available in the Chemistry parking lot at Research Drive and Towerview, and overflow parking will be available in the Bryan Center structure on Science Drive as well.

RAIN DATE – Thursday, Oct. 20.

For more information contact Kenneth Lyle, PhD at kenneth.lyle@duke.edu