Science Writers Letter from the Directorport for genetic disorders diagnosed by newborn tests....
Transcript of Science Writers Letter from the Directorport for genetic disorders diagnosed by newborn tests....
I N S C R I P TO August 2010 Science Writers Association of Emory
Dear Graduates, Faculty and friends of the GDBBS,
It is with great pleasure that we pres-ent the first Graduate Division of Bio-logical and Biomedical Sciences News-letter. This communication is intended to connect our nearly 835 graduates, over 450 current students, and hun-dreds of faculty and friends who have contributed to the astounding growth in the size and accomplishments of graduate education Emory University has seen in the past two decades.
In the late 1980s a group of visionary leaders at Emory engineered a wholesale reorganization of graduate education in the biological and biomedical sciences from departmentally based programs to an interdisciplinary umbrella program. The system that President James T. Laney, Provost Billy Frye, Deans Jeffrey Houpt and Eleanor Main, a half-dozen departmental chairs and a couple hun-dred faculty members devised is largely that which exists today. However, the
focus of students seeking the Ph.D. is now richer and more diverse. For exam-ple, the student group that is publish-ing this newsletter, the Scientific Writ-ers at Emory (SWAE), arose from the desire for a portion of our students to pursue careers in science writing. We are indebted to them for their hard work and enthusiasm in establishing this semi-annual newsletter.
We hope you enjoy the interviews with past Directors of the GDBBS, the profiles of faculty and students in each of the programs, and the opportunity to reflect on what the GDBBS has meant to you. In particular, we want you to log into your alumni account and update your record. This information is vital to our efforts to attract training grant and fellowship support and to allow us to evaluate the success of our past and cur-rent educational methods. Finally, if you are so inclined we welcome your contri-butions. In particular, we want to endow a number of named student awards to be given each year for outstanding
efforts and accomplishment. Your gift could hardly go to a more important and influential cause.
Look for the next issue in the spring.
Keith D. Wilkinson, Ph.D., Director, GDBBS
Alumni Update:http://gdbbs.emory.edu/alumniweb
Letter from the Director
GDBBS ALUMNI NEWSLETTER EDITION
Every year, GDBBS students take part in the GDBBS Student Research Symposium, presenting their data to their fellow students. This year the annual GDBBS Student Research Symposium will be held on October 5th and will include the first GDBBS Awards Banquet to be held that evening at the Druid Hills Country Club.
The Divison Student Advisory Committee (DSAC) of the GDBBS program invites students to submit abstracts of their research and present either a talk or a poster. Awards for the top three presentations in each catagories will be handed out at the end of the day.
In order to recognize students for their achievements
throughout the year, an Awards Banquet will cap off the evening. The GDBBS Awards Banquet will consist of a short reception, dinner, and a keynote address. The awards to be presented will include the awards from the Student Research Symposium, teaching awards for a GDBBS Student and Fac-ulty, and the GDBBS Mentoring award. Special recognition will be given to fellowship recipients, recent graduates, and outstanding professional and community service.
Be sure to attend this year’s GDBBS Student Research Symposium and first Annual GDBBS Awards Banquet. The Awards Banquet is sure to add to the tradition of celebrat-ing the GDBBS program already established by the GDBBS Student Research Symposium. n
GDBBS Student Research Symposium and Awards Banquet
2 I N S C R I P TO August 2010
I N S C R I P TO
Few scientists have the joy of seeing their molecular techniques lead to an actual targeted therapy. Steve
Warren, Ph.D., FACMG, who holds pro-fessorship in the departments of Bio-chemistry, Pediatrics, Human Genetics and the Winship Cancer Institute, has experienced exactly this while unravel-ing the mystery of Fragile X syndrome, the most common form of inherited mental retardation affecting one in 2000 males and one in 4000 females. Dr. Warren’s part of the story began while still a graduate student, and he truly heralded the research when he led a team of scientists at Emory Univer-sity to identify the gene responsible for this syndrome: FMR1 (Fragile X mental retardation), named for a gap on the X chromosomes observed in patients exhibiting this atypical X-linked pattern of mental retardation. This story has now come full circle from identifying the genetic cause of a disease, to the possibility of targeted treatment of the particular molecular defect.
The specific cause of Fragile X syn-drome is the expansion of a single CGG trinucleotide repeat to 200 or greater, resulting in inability of cells to produce FMRP (Fragile X mental retardation protein). Though research on this disease began with the use of pedigrees to analyze the mechanism of inheritance, we now understand the epigenetic mechanisms underlying FMR1 gene silencing, a biological phe-nomenon that was discovered in 1965, but whose functional significance was not understood until the late 90s.
F o l l o w i n g the 1991 dis-covery of the Fragile X gene, further research over the past two decades has shown that FMRP is involved in a variety of pro-cesses. mGluR5, a protein that r e g u l a t e s FMRP is cur-rently among the treatment ideas for Fragile X syndrome. The idea for using mGluR5 as a target is due to an advanced under-standing of mGluR5’s role in neuronal cell function and the discovery that an absence of the Fragile X protein leads to an overactive mGLuR5. Other treat-ment ideas include using demethylating agents such as 5-azadeoxycytidine, a
drug currently approved by the FDA for the treatment of cancer. These drugs target the source of the problem by aiming to remove the aberrant meth-ylation and therefore reactivate the FMR gene.
Dr. Warren’s accomplishments within the field of Fragile X specifically have established him as a well-respected scientist. Before moving forward to develop the Human Genetics Depart-ment at Emory University, he was an Investigator of the Howard Hughes Medical Institute for ten years. The mys-teries of Fragile X have been elucidated by taking advantage of new technolo-gies as soon as they have become avail-able, and Dr. Warren has used these
opportunities to grasp at possibilities and view systems in creative ways.
Mike Santoro and Morna Ikeda are two Genetics and Molecular Biology program graduate students currently in the Warren laboratory and can attest to the fact that the mentor in Dr. Warren is just as respected as the
scientist. His courage and energy as a mentor are evident in his relationships with trainees. Mike is impressed with his teacher and states that Dr. Warren at twice his age also has twice his energy. Both Mike and Morna feel that Dr. Warren’s “hands-off” approach allows them, as more experienced graduate students, to develop independently as scientists. In addition, due to the large size of the laboratory, there are many very skilled postdoctoral fellows, all of whom remain under the “big picture/idea generator” that Mike and Morna find their mentor to be. As Mike con-tinued to reiterate, for Steven Warren “it doesn’t matter how everyone else is doing it, we will do it right.” n
The Fragile X StoryA Brief History of Connecting Clinical Disease to Molecular Biology
Dannie perDomo
Editor in Chief: Kathryn KnoopManaging Editors: Chelsey Goins, alexander poplawsky Features Editor: Lydia morrisDesigner: nachiket KumarContact Us: [email protected]://www.students.emory.edu/sciencewriters/
Dr. Steve Warren
“The mentor in Dr. Warren is just as respected as the scientist”
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August 2010 I N S C R I P TO 3
Improved Newborn ScreeningChanging Lives Through Advances in National Screening Standards
austin Cape
All newborn babies deserve the best chance at a healthy life, and an important factor in ensuring
a thriving start to life is early disease detection through newborn screening. However, not all screenings are created equally. Surprisingly, all 50 states across the U.S. vary considerably in their man-dated newborn screening tests, diag-nostic protocols and governing policies. So why should a baby born in one state have this advantage over one born in another? The simple answer is they should not.
At Emory University in the Depart-ment of Human Genetics, Dr. Rani Singh has a vision for resolving the cur-rent patchwork of newborn screening systems. She is building strong support for what she calls “a nationally standard-ized newborn screening structure.” In fact, the U.S. Department of Health and Human Services (HHS) agreed with the concept of unifying state efforts and awarded Singh with a substantial 5-year grant to develop a solution.
As Singh explains, “Under HHS, the large scale effort being funded by the Federal Health Resources and Services Administration is a collaborative group charged with establishing a national newborn screening model system.” Further, teams in the Southeastern Regional Genetics Group (SERGG) are working to establish diagnostic labora-tory testing consistency, create a data-base directory for sample analysis and develop effective long-term follow up strategies for individuals requiring sup-port for genetic disorders diagnosed by newborn tests.
Perhaps the most well known of all metabolic disorders is phenylketonuria (PKU), a genetic disease that results in deficiency of the critical liver enzyme phenylalanine hydroxylase necessary for converting the amino acid phe-nylalanine (Phe) to tyrosine. Elevated
levels of unconverted Phe in chil-dren can cause mental retardation, slowed growth and increase the risk of seizures. Sadly, damage to babies in utero also occurs in pregnant women with PKU when mothers do not maintain a strict diet throughout fetal development.
Amazingly, doctors can treat PKU and all other metabolic disorders cur-rently screened in newborns with nutritional intervention. However, maintaining acceptable levels of Phe is a difficult task, as many common protein-containing foods such as meat, cheese and peanuts contain high amounts of the potentially toxic amino acid. Even after the critical period of development in children, physicians advise individuals to monitor blood Phe levels over their entire life. Herein lays the problem with treating metabolic diseases like PKU with diet: humans are notoriously bad lifetime dieters.
To address this dietary weakness, pharmacological agents have recently been introduced to supplement lapses in nutrition. Meghan Quirk, a Nutri-tion and Health Sciences (NHS) pro-gram graduate student in the Singh lab, is studying the efficacy of these novel treatments compared to the traditional diet management regimen. Meghan has combined her dietetic background with the study of genetic disease, and in doing so has gained experience in clinical treatment and participated in national discussions focused on improv-ing patients’ lives.
For individuals like Quirk in the field of nutrition, success is often measured by interactions with patients as much as any other factor. A striking example is the weeklong Metabolic Camp held at Emory University for females with inborn errors of metabolism. Each summer, groups of young women gather to refocus on eating habits, learn about
recent news on their disease and mingle with others struggling to overcome metabolic disorders. Quirk witnesses the enormous dedication of Singh, and says, “Rani has definitely changed the lives of many of the camp participants.”
Singh’s work not only affects patients, her ambitious work has triggered a wave of action on a larger scale. Singh proudly explains how representatives from indus-try, local universities and the national gov-ernment are anxious to get involved in the growing network of resources aiming to install national guidelines and practices for metabolic disease.
Singh’s research is a wonderful exam-ple of interdisciplinary work being con-ducted at Emory. Research scientists, medical professionals, policy makers, administrative staff and others are all contributing to a goal, wholly united and strengthened by diversity.
Striving to promote healthy children in all states is an investment in our future as well. With technologies and resources currently available, we have the power to relieve the physical, emo-tional and financial burden taxing our healthcare system. The most important question is “Do we have the will?” Singh is betting we do. n
Dr. Rani Singh
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Dangerous BugsEmory Scientists Search for New Antibiotics
justine haLL
A hospital can be a dangerous place. Patients come in for treat-ment and leave behind a variety
of infectious microbes that survive and flourish within the hospital environ-ment. Bacteria can evade disinfection regimens by forming biofilms on equip-ment or lying in a temporarily dormant state on hospital beds and furniture. Certain bacteria even live on the skin of healthy visitors and hospital staff, and later pass to immune-comprised patients. These hospital-acquired, or nosocomoal, infections are especially insidious because they tend to be more virulent and resistant to antibiotics than other pathogens.
Dr. Philip Rather, who holds an appointment in the Microbiology and Molecular Genetics PhD training pro-gram, studies two of these infections: Acinetobacter baumannii and Proteus mirabilis. Proteus has long been estab-lished as a causative agent of urinary tract infections while Acinetobacter is an emerging pathogen associated with an increasing spectrum of diseases. Both infections transmit diffusible chemical signals between cells and direct their d i f f e r e n -tiation as a result. This b a c t e r i a l communica-tion system, known as quorum sensing, has recently been recognized as an ideal target for antibiotic drugs due to its potential in stopping infections at an early stage.
Dr. Rather recently discovered a new quorum sensing molecule in Acineto-bacter and is now investigating the specificity of its signal. Bacteria trans-mit and receive these chemical signals in microbe-laden human tissues, such as the intestine. Some molecules are spe-cific to one strain or species of bacteria while others transmit general messages that can be received by many species. Human to bacteria communication is
even possible as “Salmo-nella can clearly recognize epinephrine and norepi-nephrine,” two hormones released by human cells, Dr. Rather explains. Under-standing the specificity of the Acinetobacter signal helps indicate the message being sent. If Dr. Rather’s newly discovered quorum sensing molecule is specific to Acinetobacter, it could be a viable target for drug development. For example, an antibiotic could contain a molecule similar to Dr. Rather’s target that could block harmful bacterial mes-sages and stop Acinetobacter growth without interfering with human cell function.
Proteus mirabilis is another bacte-ria sending and receiving messages in the human body. Normally a vegetative swimmer cell with a few small flagella, tail like appendages that aid in movement, Proteus transforms into a swarmer, a cell that is 20 – 40 times longer and
has up to 50 times more flagella, when it contacts a solid surface. When enough
swarmers are present, they intertwine their flagella and further transform into what Dr. Rather calls “a moving biofilm.” The biofilm is much more dangerous than single Proteus cells because it can invade new tissue, is more resistant to antibiotics and produces more virulence factors. Another unpleasant result, Dr. Rather notes, is the production of putrescine and cadaverin, two signaling molecules responsible for the character-istic odor of urinary tract infections.
Randy Morgenstein, one of Dr. Rath-er’s graduate students, is investigating how Proteus cells recognize a surface
and translate this stimulus into gene expression changes. He has found that a common outer membrane protein, O-antigen, is required for swarmer dif-ferentiation. O-antigen, however, does not interact directly with the attach-ment surface, but instead works by regulating flagellum synthesis. This discovery, combined with previous work from the Rather lab, has revealed Pro-teus as a bacterium with a large number and unique organization of motility and adherence genes. As stated in one of Dr. Rather’s recent papers, “the decision to stick or swim is central to the lifestyle of this opportunistic pathogen.”
Discoveries such as these are an important step towards translating and understanding the bacterial communi-cation system. In the case of Acineto-bacter and Proteus, further understand-ing may mean new and more specific antibiotics. However, Dr. Rather is quick to emphasize that “the most important findings in science are from basic sci-ence,” and he will continue in that direc-tion by investigating the regulation of Proteus swarming behavior. n
“the most important findings in science are from basic science”
Dr. Philip Rather
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August 2010 I N S C R I P TO 5
Neuroscience research generally starts with a brain. And for those interested in social behavior,
there are few brains better suited for study than that of the prairie vole— suited because the prairie vole belongs to the less than 5% of mam-mals that form monogamous pair-bonds. This is in contrast to other closely related species such as the meadow vole that are not monogamous and not even very social. Work in Dr. Larry Young’s lab has focused on identifying differences between the brains of these rodents in order to determine what gives rise to the behav-ioral differences. Evidence points to two neuropeptide systems, oxytocin and vaso-pressin, that seem to play large roles in the control of social behavior. The expression pat-terns of the peptide receptors, which sense these neuropep-tides, contrast greatly between species. Injecting antagonists for these receptors into cer-tain brain regions prevents prairie vole sociality. The social behaviors exhibited by the prairie vole therefore rely on the presence of these receptors in specific regions of the brain. Before the receptors can perform their functions however, the peptides themselves must be secreted by neurons that respond to social stimuli.
Neuroscience student Meera Modi is interested in using the prairie voles as a model in which pharmaceutical compounds can be tested for their ability to influence social behavior. Efficacious drugs could serve as treat-ments for disorders characterized by deficits in sociality such as autism. She has already begun testing two com-pounds that are already approved for clinical use: D-cycloserine, an allosteric modulator of NMDA receptors, which
might facilitate social recognition, and Melanotan II, which has receptors on oxytocin-expressing cells, and could therefore increase oxytocin signaling in people who are less responsive to social stimuli. Reflecting on the translational
nature of her work, Meera notes, “We all try to convince the NIH that our work has important translational relevance, but it’s great to be working on a proj-ect where the implications for treating human disease are so apparent.”
Prairie voles offer a natural system in which to study disorders of social behav-ioral systems, but researchers have until now lacked the genetic resources needed for the sorts of translational work that occurs commonly in mice. Collaborating with Dr. James Thomas from the PBEE and GMB programs, the lab has recently begun developing prairie vole genetic resources. Katie Barrett, another Neuro-science student, has taken advantage of some of these resources as she develops
a transgenic prairie vole with V1a vaso-pressin receptor knockdown using RNA interference. As opposed to a knockout animal, the knockdown will still express low levels of the protein, within a range of what is naturally observed. These
knockdown animals will help validate previous work, as well as offer opportunities to explore socio-developmental aspects of the gene. In the future, Katie plans to take her transgenic animals into semi-natural enclo-sures in order to study the role the socially relevant gene plays in an ecological context.
The members of the Young lab understand the importance of social bonding. There are numer-ous lab outings, including an occasional bowling day and an annual trip to Dr. Young’s cabin in South Georgia. As anyone on the 5th floor of Yerkes can attest, the lab can tend towards the ridiculous sometimes. Like the time the lab held a mustache growing competition, featuring fake mustaches for facial-hair challenged individuals.
More recently, some members of the lab took part in a flash dance mob at Piedmont Park. The basic idea of a flash dance mob is that a group of people gets together and practices a dance in secret before performing the dance seemingly spontaneously in the middle of an unsuspecting crowd, though this was surely not the first time the Young lab has surprised a crowd. The Neuroscience program itself offers many opportunities for socializing out-side the lab. The Graduates in Neurosci-ence (GIN) program government orga-nizes Neuroscience mixers throughout the year as well as an annual late-August retreat to welcome incoming students. These socials help keep up friendships within and between labs as well as share ideas and foster collaborations. n
Working with Dr. YoungHow I Learned to Have Fun While Studying the Bond
LaniKea KinG
Dr. Larry Young holding a prairie vole
PHOTO: JACK KEARSE/EMORY UNIVERSITY
6 I N S C R I P TO August 2010
A proud member of the Emory fac-ulty in the Department of Cell Biology for nearly 30 years, Dr.
Winfield Sale had a hand in the found-ing of the Biochemistry, Cell and Devel-opmental Biology program. Dr. Sale explains that the Cell Biology Program was initially established in 1989 and was later expanded to include Develop-mental biology. The program was finally fused with the Biochemistry Program to form what is known today as the Biochemistry, Cell and Developmental Biology program (BCDB).
Research in the Sale lab, which has been supported by an NIH MERIT Award and grants from the March of Dimes and American Cancer Society, utilizes the model genetic organism Chlamydomonas, a green algae, to study the highly conserved pathways that regulate molecular motors and movement of cilia, whip-like append-ages found on the cell surface. “The work on cilia has led to study of cell signaling mechanisms that target and anchor oth-erwise ubiquitous kinases (PKA, CK1) and phosphatases (PP1, PP2A) in the cell,” explains Dr. Sale. When asked about the impact of his work, which has made him a forerunner in the fields of ciliary motility and dynein motors, Dr. Sale notes, “due in part to Chlamydomo-nas, we have experienced a revolution in our under-standing of the universal role of cilia in cell signaling and motility, mechanisms important to human devel-opment and function of most organs in the adult.”
Dr. Sale runs a laboratory full of excited and interested graduate stu-dents and post-doctoral fellows. He was awarded the GDBBS Graduate Mentorship Award in 2001, illustrating
his commitment to train-ing and to the graduate programs. Dr. Sale states, “I am a strong proponent of hosting underrepre-sented minority students, including students from Morehouse and Emory during the summer S.U.R.E. program offered here at Emory.” He has also actively participated in interna-tional collaborations and has recently invited a post-doctoral fellow from The University of Tokyo to join him at Emory.
Rasagnya Viswanadha, a second year BCDB gradu-ate student in the Sale lab, is originally from Toronto, Canada, where she received her bachelor’s degree in Bio-chemistry. What Rasagnya likes most about her thesis project is that it is interdis-ciplinary and has required her to learn a “wide range of experimental techniques in genetics, biochemistry, molecular biol-ogy, microscopy and cell biology.” Spe-cifically, Rasagnya is studying how large multi-subunit ciliary dynein motors are assembled, transported and localized
in the ciliary axoneme, the structural backbone of cilia, to further understand the underlying mechanisms of motility.
Rasagnya praises Dr. Sale’s mentor-ship and training, stating “In addition to getting excellent training in hypothesis
design and experimental techniques, Dr. Sale and the lab personnel are extremely helpful in teaching me how to write.” She notes how important these skills are as a scientist and commends having
been afforded the opportunity to attend confer-ences, present posters, and apply for grants. Rasa-gnya is very grate-ful for the immedi-ate help and advice. Recently, Dr. Sale
even moved from his spacious office down the hall to a desk inside the lab—highlighting his commitment to stu-dents and his love of science. n
Advancing the Field of Cell MotilityUsing Cilia to Understand General Mechanisms of Cell Signaling
mariana manDLer
Dr. Winfield Sale and Rasagnya Viswanadha
“we have experienced a revolution in our understanding of the universal role of
cilia in cell signaling and motility”
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August 2010 I N S C R I P TO 7
The Graduate Division of Biologi-cal and Biomedical Sciences at Emory University has produced
a prodigious number of PhDs in the past 20 years, 835 to be exact. Among Emory graduates who have chosen to make their career at Emory is Dr. Ifor Williams, a full-time Clinical Pathol-ogy faculty member functioning as both a clinician and prin-cipal investigator. As a graduate stu-dent Dr. Williams investigated the mechanisms of transplant survival and acceptance or rejection of the tissue by the Major Histocompatibility Complex or MHC restriction.
The Williams lab has just a few mem-bers; the small size of the lab facilitates a very cozy and personal atmosphere. Dr. Williams, in fact, prefers to be called Ifor by lab members and on most days he will frequently be found familiarizing himself with the day-to-day progress of the lab. Kathryn Knoop, a student in the Williams lab, is in her fourth year in the Immunology and Molecular Pathogenesis graduate program. She is currently investigating the role of RANK ligand (RANKL), which is a member of the TNF-superfamily of cytokines in the mucosal immune system.
In the past decade, our understand-ing of the importance of the mucosal immune system, a major part of the gastrointestinal (GI) tract, has increased significantly. In fact, over half of the effector cells of the immune system reside in the GI tract, which often serves
as an interface between host and patho-gens. In addition to traditional effector cells of the immune system such as T and B-cells, macrophages and dendritic cells, the gut is home to a highly special-ized class of immune surveillance cells called M-cells. M-cells have the ability to capture and present large particu-
late antigens to the cells of the mucosal immune system.
The study of M-cells now dominates the research in the Williams lab. So far, Kathryn has shown that the cytokine RANKL is both necessary and sufficient for the proper development of M-cells. New developments in M-cell research have been few and far between, but her work has lead to a paradigm shift in M-cell development with the findings that B-cell signals are not required for the development of M-cells, as previ-ously thought. Her current findings suggest commensal bacteria may play
a role in the life-cycle of M-cells. Dr. Williams takes pride in these findings because they were the result of the col-laborative effort between him and the students he mentors. Dr. Williams no longer performs his own experiments, but likens students to “his hands at the bench” and describes current projects
as “a marriage of ideas”. While dif-ficult, and some-times frustrat-ing, Dr. Williams thoroughly enjoys mentoring PhD students. “They are a lot of fun to work with, and I am excited to see what they can do at the bench,” he explains.
In addition to advancing the basic understand-ing of immunol-ogy, Dr. Williams
has recently become involved in the recruitment of new students into the IMP program. As a member of the IMP
Executive Committee he has made increased diversity one of the main goals of the pro-gram. When asked if diversity was an important consider-ation in recruitment Dr. Wil-liams responded, “There is no
reason science should remain a bastion of a bunch of white guys running things from the top.” This type of thinking is becoming more prevalent in the scien-tific community, and many believe that increasing diversity will lead to new dis-coveries due to the novel perspectives that minority researchers provide. n
Immunology of the Digestive SystemEmory Graduate Mentors Next Generation of Immunologists
Danny rios
Dr. Ifor Williams with Kathryn Knoop
PHOTO: CHERYL HO
“There is no reason science should remain a bastion of a bunch of white guys running
things from the top.”
8 I N S C R I P TO August 2010
When a group of Emory professors, including Dr. Eddie Morgan,
saw a need for a more pharma-cology and toxicology-heavy course of study, the Molecu-lar and Systems Pharmacology (MSP) program was developed, replacing the former Physi-ological and Pharmacological Sciences program in the early nineties. Their foresight has played a major part in Emory University’s rating as the #1 university in the world for impact in the fields of phar-macology and toxicology by “The Scientist” magazine.
Though he does not currently have any graduate students working in the lab, Dr. Morgan has been director of the MSP program for the past eleven years and served as the director of graduate studies for four years prior. Through his position as director, Dr. Morgan inter-acts with students on a daily basis. Three PhD students have graduated from his lab at Emory, and he also supervised two graduate students while serving as a visiting scientist at the Karolinska Institute. He describes working with students as “one of the most gratifying things about [his] job”, and details that his participation in graduate programs is often more rewarding than research because of its constant gratification. “When experiments aren’t working and you’re worried about grants…it gets you through the down times,” he explains.
Despite the inevitable “down times”, Dr. Morgan’s research on the cytochrome P450 superfamily of enzymes—which play diverse roles in the oxidation of organic substances—has led to some very interesting findings.
Since coming to Emory in the early eighties, a major focus of Dr. Morgan’s
research has been on how inflammation or inflammatory diseases affect P450 expression. “I’m interested in their regu-lation because changes in expression can affect the response to both thera-peutics and toxins.” Most cytochrome P450 enzymes are downregulated by inflammation, and “the consequence is a person who is undergoing an inflam-matory response due to infection…will have decreased clearance of some drugs, which can result in the buildup of the drug in the blood and toxic con-sequences,” he elaborates. Ultimately, research in the Morgan lab aims to identify which P450s could be novel therapeutic targets in inflammatory dis-ease. The Morgan lab has also formed collaboration with Dr. Dan Kalman in
the Department of Pathology, which involves work on a rodent model of enteropathogenic E. coli (EPEC) infec-tion. This is an important area of research as evidenced by many large scale food poisoning incidents that have recently hit the news. These infections can be fatal, especially in babies and the
elderly. Drs. Morgan and Kalman have found that infection with Citrobacter rodentium, a mouse pathogen similar to EPEC, leads to the selective downregulation of seven different P450s in the liver. They are interested in whether this downregulation plays a physiological role in the host response to infection, and how this downregulation poten-tially affects drug metabolism.
Even when he is traveling to speak about the importance of his research at conferences across the country, Dr. Morgan still has students in mind. “I try
to go visit an HBCU [historically black college or university] once a year to make contacts; I also encourage other faculty to do it.” His active involvement has helped the MSP program and the GDBBS to identify and recruit talented minority students who are successful in scientific research careers.
When asked about the medical impli-cations of his work, Dr. Morgan explains “it has some application to therapeu-tics…clinicians realize they ought to look out for different drug responses in patients with inflammatory dis-ease.” Understanding P450 expression in disease also gives drug companies and the FDA an idea of the possibili-ties regarding patients’ response to
different drugs. “You can never underestimate the power of basic research…time and time again sci-entists are following their specific interests and the [health implication] of
their findings becomes very apparent.” Dr. Morgan’s research is a great example of how basic research and collaboration can result in practical applications for fundamental scientific discoveries. n
P450s and Drug PharmacologyUsing Research and Mentorship to Advance the Field of Pharmacology
LyDia morris
Dr. Eddie Morgan
PHOTO: CHERYL HO
“You can never underestimate the power of basic research.”
August 2010 I N S C R I P TO 9
As its name implies, the Population Biology, Evolution, and Ecology (PBEE) program spans multiple
scientific disciplines, and the research of PBEE faculty member Dr. Todd Schlenke encompasses aspects of all three. The Schlenke lab uses Drosophila melano-gaster, more commonly known as the fruit fly, as a model organism to better understand evolutionary genetics and host–parasite relationships.
One particular natural enemy of fruit flies is the parasitic wasp. The wasp injects its eggs into developing flies, and uses the nutrients from the fly eggs to support the development of its own eggs. Dr. Schlenke’s research uses this host-parasite relationship to gain insight into general mechanisms of innate immunity, a non-specific attack on infecting organisms used as a first line of defense. The Schlenke lab has collected several wasp species known to infect fruit flies and uses these wasps to study both the cellular immune response of the fruit fly to invading pathogens and the mecha-nisms employed by the wasp to evade the host’s immune response.
PBEE graduate students Neil Milan and Erin Keebaugh focus on different aspects of the fly immune response. Like us, all wasps and flies are Eukaryotic, and unlike bacteria, we all have true nuclei and therefore similar cellular organiza-tion and perhaps function. Specifically, Neil studies the fly-pathogen relation-ship on an organismal level, focusing on the transfer of genetic information between fruit flies and the pathogenic wasps that invade developing fly eggs. Neil states he is “trying to unravel the extent and potential causes of this phenomenon within the fruit fly-wasp interaction” because wasps can carry and transfer fly diseases much like mos-quitoes carry and transfer diseases to humans. Dr. Schlenke believes his work could have a huge impact on the field.
Erin, however, is researching the evolution of fruit fly genes over time in search of genes that regulate its immune response. The lab has used genetic mapping to characterize genes that are upregulated in fruit flies during wasp infection, and Erin is studying the immunological importance of those can-didate genes. Since wasps and fruit flies are both insects, understanding how they can distinguish between invading wasp cells and their own cells could lead to a better understanding of human immune responses to similar para-sites, including those responsible for human diseases such as malaria, Giar-diasis, and African Sleeping Sickness. Dr. Schlenke stays connected with the research of his students through weekly individual meetings as well as group lab meetings and even helps “dissect flies when a lab member needs an extra pair of hands.” As Erin says, “Dr. Schlenke is always around and willing to help” and is
“enthusiastic about the research going on in his lab.” Similarly, Neil describes Dr. Schlenke’s personality as keeping “the lab full of serious discussions and random laughter, often inter-mixed.” While the lab is dedicated to understanding fruit fly immunity, Dr. Schlenke also makes sure they have time for extracurricular activities in order to stay well rounded as a group and as individuals. Bowling and ice skating are just a couple of the activities the lab has participated in as a group, keeping them connected on more than just a profes-sional level. In addition, Neil Milan, a Phillipino student himself, helps the GDBBS recruit other minority students to its programs. n
The Fruit Fly and the Parasitic WaspExamining the Host-Parasite Relationship
mary puCKett
Graduate student Neil Milan with tubes of Drosophila Melanogaster
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10 I N S C R I P TO August 2010
3 Questions What Former GDBBS Directors Had to Say
CheryL ho
We spoke to three previous Directors of the Graduate Division of Biological and Biomedical Sciences (GDBBS) about their goals for the Division and how it has evolved through the years.
Dr. Donald Humphrey was the founding Director of the GDBBS, serving from 1988 to 1990. His major research interests include brain mechanisms of voluntary movement control and long-term brain responses to disconnection injuries, such as spinal cord injury. Dr. Humphrey has served as the Dean for Research in Emory’s School of Medicine and has pioneered studies using neuronal signals for controlling limbs and other prostheses. He is currently a Professor and Deputy Chair in Emory’s Department of Physiology.
Senior Science Advisor for Emory’s Division of Educational Studies and C.H. Candler Professor of Cell Biology Emeritus Dr. Robert DeHaan served as GDBBS Director from 1989 to 1991. Dr. DeHaan’s research interests at the time were biophysics and developmental biology of cardiac cells. His research has since shifted to science education – tackling the question of how teaching can be improved so that “students recognize the excitement and intellectual challenge of science.”
The GDBBS Director from 1991 to 2003 was Dr. Bryan Noe, who served as faculty in Emory’s department of Cell Biology. Before he held this position, Dr. Noe was the Director of Graduate Studies for his home depart-ment for over 10 years. His primary research interests focused on posttranslational processing of peptide hor-mone precursors. Dr. Noe is currently Dean of the Graduate School at the University of Alabama at Birmingham. • What were your major goals for the GDBBS while you served as Director?
Dr. Donald Humphrey: [My primary goal was] to develop a new set of interdisciplinary programs in the biological and biomedical sciences that more closely matched current research interests nationally, and that would strengthen our already excellent faculty’s role in graduate education in these areas.
Dr. Robert DeHaan: The Division was created a year earlier, in 1988, under the interim leadership of Dr. Don Hum-phrey. My goals when I took over in 1989 were to help bring about the transition from a departmental structure to an interdepartmental program, to define the relative roles of the faculty in their departments and in the Division, and to foster the transfer of recruitment and training of graduate students from the departments to the Division.
Dr. Bryan Noe: The major goals were to increase the number and level of preparedness of applicants to GDBBS programs, increase the number of funded training grants which would provide student support to supplement that provided by the Graduate School and the School of Medicine, to actively engage faculty, program directors and department chairs in developing those policies and procedures, [and] to the extent possible, provide infrastructural support from the GDBBS office to assist programs in providing the best possible educational experience for GDBBS students. Although the approaches to reaching these goals had to be modified over time as the number of faculty and students in GDBBS programs grew, the basic focus remained the same.
•• What changes in the Division did you implement, or what new areas did you oversee development of, during this time?
DH: When the GDBBS was formed in 1988, the basic science departments at Emory were down to 36 applications across 7 departments for graduate admission. Within 4 months after I was asked to form the Division by Dr. Billy Frye, then Dean of the Graduate School and Vice President for Research, we (my secretary, my lone recruiter, and I) had written the operating handbook for the Division and edited all of the Peterson’s Guide descriptions for six new interdisciplinary programs in the biological and biomedical sciences that our excellent faculty had written.
I must admit that it was quite a task talking our faculty into abandoning their departmentally based programs for devel-opment of new interdisciplinary programs – a bit like trying to herd cats – but they responded like the real champions that they are and we made the Peterson’s guide publication deadlines. By 1989, we had over 90 new applicants to our programs, and the entering GRE score had improved by 100 points. The GDBBS was on its way!
August 2010 I N S C R I P TO 11
I also made one other, very important change: I persuaded the Divisional faculty and departmental chairs to extend graduate status to our major clinical departments. Prior to this time, a member of the graduate school faculty in a clinical department had to hold a cross appointment in a basic science department in order to have PhD students. This excluded many good investigators from access to good graduate students and vice-versa. The change was approved, and now our graduate education programs in the clinical departments attract many good students who aid in the translation of bench research to clinical applications.
RD: When I completed my two-year term in 1991, we had made a good start in accomplishing all the above goals. The Division was left in a much stronger and more highly organized state for the next Director, Dr. Bryan Noe.
BN: There were numerous policy and procedure changes during the period of time I served as GDBBS Director, too many to recount in detail. So let me point to two that I regard as perhaps being most significant; changes that may have had a positive impact on growth of the Division. These were not changes that I alone was individually responsible for imple-menting. Making these changes was always a collective effort that resulted from discussions with and contributions by faculty, program directors, chairs, and GDBBS office staff members. Possibly the most significant change that occurred during my term as Director was the development of the FileMaker Pro database system for management of applica-tions, admissions, and tracking of student progress during their course of training, and placement after receiving their degrees. An offshoot of this data management system was developed to assist program faculty with the preparation of NIH T32 training grant applications. Together, the application of these FileMaker databases facilitated data manage-ment, and in particular helped to promote submission of more training grant applications. When I started as GDBBS Director in 1991, there was only one training grant available to support GDBBS students. Today, I believe the total number of training grants held by GDBBS faculty is nearing 20. [There are currently 20 institutional training grants that directly support GDBBS students.] Another significant change that was implemented with input from the program Directors was the development of a formulaic approach to distribution of internal resources to the programs. This approach incorporated an incentive for programs to apply for and secure training grant funding. Together, these changes were largely responsible for making it possible to recruit and support larger numbers of students in GDBBS programs.
••• What do you think is the most beneficial asset of being a student in the GDBBS?
DH: Access to a wider range of highly qualified faculty mentors, a wider range of dissertation subjects, opportunities to engage in applied as well as basic biological and biomedical research, and support from a top-notch educational institu-tion. These are indeed golden opportunities not only for students in the GDBBS, but also for the excellent divisional faculty who mentor them and help to pay for their stipends and dissertation research costs.
RD: There is ample evidence that the most exciting research often occurs at the interface between fields. A student in the Division now has greater opportunities for interdisciplinary work and broader choices among a wide selection of courses and of research advisors than was possible under the previous departmental structure.
BN: To answer biological questions, a successful bioscience researcher must be in a position to apply every possible tool in the research toolbox. Since no one investigator could possibly master the use of every research tool, science by nature has to be collaborative. Accordingly, if one is training to become an independent investigator, then he/she should be exposed to the collaborative approach to research from day one in the educational process. That is the approach that interdisciplinary graduate programs provide. n
“Some Scientists Doubt the Value Of ‘Genetic Finger-print’ Evidence” January 29, The New York Times
“Troubles Continue to Plague Orbiting Hubble Tele-scope” June 15, The New York Times
“F.D.A. Approves Radical Gene Therapy for Advanced Cancer” November 14, The New York Times
“Science Fiction Nears Reality: Pocket Phone for Global Calls” June 26, The New York Times
“First Africanized Bees Are Trapped in U.S.” October 18, AP
“Telomeres shorten during ageing of human fibro-blasts” May 31, Science
“Direct gene transfer into mouse muscle in vivo” March 23, Science
“Reversal of experimental parkinsonism by lesions of the subthalamic nucleus” September 21, Science
Headlines from 20 years ago
12 I N S C R I P TO August 2010
BCDB
Karen Newell-Litwa phD Grove City College
Bryn Moore ms moravian College
Avanti Gokhale phD s.r.m. arts & science College, pondi-cherry Central university
Seth Kelly phD Grove City College
Rebekah Kushner phD George Washington university
Robert Lyng phD harvard university
Rebecca Sanders phD/mD agnes scott College
GMB
Andrea Kasinski phD suny, Buffalo
Mary Lucas phD Virginia union university
Anjali Shah phD Vanderbilt university, johns hopkins university
Carolyn Beam phD Wake Forest university
Lyra Griffiths phD agnes scott College
Rebecca Iskow phD university of maryland, College park
IMP
Shana Coley phD/mD auburn university
Andrea Siegel phD Brandeis university
Sean Stowell phD/mD Brigham young university
Kathleen GrayphD university of michigan
Michael Lo phD university of California, san Diego
MMG
Jeffrey Mercante phD southern methodist university, Louisiana state university
Nazia Kamal phD university of California, riverside
Patrick Reeves phD university of Georgia
Liang Shang phD nanjing agricultural university, Fudan university
MSP
Jill Dunham phD university of Georgia
Hasan Irier phD ankara university, Georgia state university
Alicia Lyle phD Georgia institute of technology
NHS
Reena Oza-Frank phD ohio state university, university of tennessee
NS
Albert Davis phD/mD emory university
Zoe Donaldson phD university of California, Los angeles
Jun Liu phD Beijing Foreign studies university, Georgia institute of technology
Rebecca Rosen phD yale university
Anna Wiste phD/mD Columbia College
Rayna Bauzo phD Florida state university
Lindsey Fischer phD/mD emory university
Yair Gozal phD/mD Case Western reserve university
John Rolston phD/mD Columbia university
PBEE
Omar Cornejo phD universidad simon Bolivar-Caracas, iViC
Karyn Steinberg phD northwestern university
Recent Graduates
August 2010 I N S C R I P TO 13
BCDB
Megan Allen Bs, university of Georgia Dawn Barnes Bs, university of arizona ms, arizona state university
Chantel Cadwell Bs, Georgia state university
Emily Kuiper Bs, pennsylvania state university
Laura Newman Bs, indiana university, Blooming-ton
Marc Schureck Bs, university of Florida Wenji Su Bs, hong Kong univ sci tech
Jadiel Wasson Bs, university of Georgia
GMB
Benjamin Barwick Bs, ms, Georgia inst technology
Sarah Bay Ba, harding university Rick Bienkowski Bs, state university of ny at stony-Brook
Darwin Hang Bs, university of minnesota, min-neapolis
Sasha Parets Bs, Brandeis university Benjamin Rambo-Martin Bs, ms, university of Georgia Brooke Weckselblatt aB, Bryn mawr College
IMP Rakieb Andargachew Bs, Lafayette College ms, Georgia state university Alexander Bally Ba, university of Colorado, Boulder Lara Beers Bs, university of Georgia Ankita Chowdhury Bs, university of maine, orono Christopher Cutler Bs, Brigham young university Megan Hinkley Bs, texas a&m university, College station
David Holthausen Bs, Boston College
Shardule Shah Bs, Case Western ms, university of pennsylvania MMG Erica Bizzell Bs, towson university Martin Deymier Bs, university of arizona William Kaiser III Ba, university of Georgia Jia Meng Bs, Wuhan university ms, Cal state univ, Los angeles Max Schroeder Ba, ohio Wesleyan university
Kellie Vinal Bs, north Carolina state university, raleigh
Morgan Waddles Ba, ohio Wesleyan university
MSP Nicole Brown Ba, William jewell College
Ellen Heath Bs, university of south Carolina, Columbia
Ayush Kishore Bs, California state university
Min-Young Lee Bs, ms, Kyungpook national uni-versity
Gina Lenzi Bs, university of Virginia
Richard Stanton Bs, Georgia institute of technology ms, Georgia state university
Brandon Stauffer Bs, university of the sciences, philadelphia
Kristen Stout Bs, Brigham young university
Jacob Winschel Bs, university of pittsburgh
Philip Zakas Bs, elon university
NHS
Kathryn Coakley Bs, ms, Case Western reserve uni-versity
Unjali Gujral Ba, university of California, irvine mph, yale university
Shin Kim Ba, mph emory university
Memorie Nichols Bs, auburn university ms, Weill Cornell Graduate school
Karen Siegel Ba, university of penn mph, yale university
continued on pg 14...
Incoming Students
14 I N S C R I P TO August 2010
NS
Jabari Bailey Bs, morehouse College
Termpanit Chalermpalanupap Bs, emory university
Paul Evans Jr. Bs, emory university
Kevin Fomalont Ba/Bs, penn state university
Michelle Giddens Bs, Worcester state College
Thomas Hennessey Bs, allegheny College
Lukas Hoffmann Bs, university of pittsburgh
Laura Jones Bs, haverford College
Tyra Lamar Ba, north Carolina Central univer-sity
Kelly Lohr Bs, Dickinson College
David Nicholson Bs, university of south Florida
Samuel Rose Bs, university of Georgia
Karl Schmidt Bs, Davidson College
Iris Speigel Bs, university of maryland, College park
Andrew Swanson Bs, Georgia state university
Kristen Weiss Bs, Binghamton university
Bethany WilsonBs, College of William and mary
Kelsey ZimmermannBs, emory university PBEE
Brooke Bozick Bs, penn state
Sarah Anne Guagliardo Bs, George Washington university mph, yale university
Amanda Pierce Bs, university of Kansas
Gayatri Sekar Bs, srm university
MD/PhD StudentsBCBD
Daniel Barron Bs, university of California, san Diego
Benjamin Nanes Ba, Washington university, st. Louis
Jennifer Rha Ba, university of pennsylvania
IMP
Duke Geem Ba, Boston university
Rebecca Markovitz Ba, yale university
Nina Salinger Bs, haverford College
NS
Patrick Mulligan Bs, emory university
PBEE
Joshua Shak Ba, amherst College
Incoming... continued from pg 13