This is the twice-per-month electronic newsletter for basic, preclinical and translational research news related to the Johns Hopkins School of Medicine. Please forward freely. Direct comments or questions to Joanna Downer, PhD, in the Office of Corporate Communications (4-5105, jdowner1@jhmi.edu).
IN THIS ISSUE:
+Biological Trick Reveals Key Step in Melatonin's Regulation
+Genetic Aberration Helps Explain Variation in Cystic Fibrosis
+Region of Chromosome 1 Important in Blood Pressure Regulation
+Skin Cholesterol Indicates Presence of Plaque Build-Up in the Heart
NEWS BRIEFS:
Panel Reports Conclusions on Embryonic Stem Cell Safety and Justice
Two-Day Grant Writing Workshop Starts Dec. 9
Hirschi to Present Vascular Cell Engineering Seminar Dec. 5
University-Wide Conflict of Interest Training Deadline Dec. 31
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RESEARCH HIGHLIGHTS:
10/26/03
Biological Trick Reveals Key Step in Melatonin's Regulation
Johns Hopkins researchers have uncovered a key step in the body's regulation of melatonin, a major sleep-related chemical in the brain. In the December issue of Nature Structural Biology, the research team reports finding the switch that causes destruction of the enzyme that makes melatonin -- no enzyme, no melatonin.
Melatonin levels are high at night and low during the day. Even at night, melatonin disappears after exposure to bright light, a response that likely contributes to its normal daily cycle. To help understand melatonin's light-induced disappearance, the Hopkins researchers turned to the enzyme that makes it, a protein called AANAT.
One way cells turn proteins like AANAT on and off is by attaching or removing bits such as phosphate groups to particular positions in the protein. For AANAT, the key modification spot turns out to be building block number 31, the researchers discovered.
"We found that addition and removal of the phosphate group at this position is the key step in regulating the enzyme's stability," says Philip Cole, MD, PhD, professor and director of pharmacology and molecular sciences in Hopkins' Institute for Basic Biomedical Sciences. "When this phosphate group is present, the enzyme is stable."
To test the importance of the phosphate group to the enzyme's stability, research associate Weiping Zheng, PhD, developed a mimic of the key building block, a threonine, with the equivalent of a permanently affixed phosphate group.
More Info
Nature Structural Biology Dec. 2003;10(12):1054-1057 (published online Oct. 26)
11/6/03
Genetic Aberration Helps Explain Variation in Cystic Fibrosis
In two presentations at the annual meeting of the American Society for Human Genetics in Los Angeles, Hopkins researchers revealed the existence of specific short repeats of particular genetic building blocks in the gene at the root of cystic fibrosis (CF), an inherited and often fatal lung disease. The researchers also showed how the repetitious pattern may help predict the disease's severity.
CF stems from mutations in a gene called CFTR, or cystic fibrosis transmembrane conductance regulator. When specific mutations appear in both copies of the gene, a sticky mucus builds up in the lungs, making breathing difficult and trapping bacteria that can cause serious and deadly infections.
One CFTR mutation, known as 5T, doesn't always cause CF -- even when 5T and one of the traditional CF-causing mutations are present, a person can be disease-free. However, there's no good way to predict whether the 5T combo will lead to disease or whether the person will be perfectly healthy.
Tim Hefferon, a graduate student working with Garry Cutting, PhD, reported at the meeting that certain length combinations of T and TG repeats in CFTR are more likely than others. In a subsequent presentation, fellow graduate student Josh Groman reported that TG repeats of 12 or 13 sets are more common in people with 5T and a CF-causing mutation and lung disease than in those who have the mutations but are healthy.
ASHG annual meeting, Abstracts 75 and 235
11/8/03
Region of Chromosome 1 Important in Blood Pressure Regulation
At the American Society for Human Genetics annual meeting in Los Angeles, Hopkins research associate Yen-Pei Christy Chang, PhD, presented evidence that a region of chromosome 1 is involved in appropriately regulating blood pressure.
The scientists conducted a genome-wide analysis of 1,875 people in 585 families collected through the GenNet network of the National Heart, Lung and Blood Institute's Family Blood Pressure Program. Through their analysis, the scientists linked a region containing more than 200 known genes to blood pressure. The researchers also highlighted 24 genes whose functions might predict some role in hypertension, and closely examined nine of these genes. In three of these nine, their work uncovered single nucleotide polymorphisms (SNPs) that were associated with hypertension.
This region of chromosome 1 has been linked to related disorders such as type 2 diabetes and to a condition called familial hyperlipidemia (in which levels of cholesterol are high). However, this is the first analysis to identify candidate genes for additional study and to offer good evidence that more than one gene in the region is involved in blood pressure regulation, says the study's principal investigator, Aravinda Chakravarti, PhD, director of the McKusick-Nathans Institute of Genetic Medicine.
More Info
ASHG annual meeting, Abstract 244
From the Clinic:
11/10/03
Skin Cholesterol Indicates Presence of Plaque Build-Up in the Heart
The amount of cholesterol found in skin cells may be a good indicator of the presence of plaque build-up in the heart, Johns Hopkins researchers reported at the 76th Scientific Sessions of the American Heart Association, held in Orlando.
Researchers looked at 222 healthy adults ages 45 to 84. They took blood samples from the participants and determined their level of coronary artery disease using helical computed tomography (CT) and other tests. They also measured the level of cholesterol in the participants' skin, using a simple dye test on the palm of the hand.
The Hopkins team found that skin cholesterol was significantly correlated with the presence of early coronary artery disease, but was not associated with the level of blood cholesterol, a common unit of measure for heart disease.
"People who have low blood cholesterol think they're healthy, but some may have undetected heart disease," says Dhananjay Vaidya, PhD, lead author and a postdoctoral cardiology fellow. "This test gives us an independent and early measure of the health of the heart."
The association between skin cholesterol and coronary artery disease was stronger among whites than African-Americans, Vaidya says, but at this point researchers don't know why.
Panel Reports Conclusions on Embryonic Stem Cell Safety and Justice -- The human embryonic stem (ES) cell lines currently eligible for research with federal funds are not suitable for use in future clinical trials, nor would they ensure fair access to new stem cell based therapies, according to the scientists, philosophers and lawyers on a panel convened at Johns Hopkins. The panel's conclusions appear in the November issue of Fertility and Sterility and in the November/December issue of The Hastings Center Report. The panel, known as the Working Group on Criteria for Cell-Based Therapies, was led by Ruth Faden, PhD, MPH, and John D. Gearhart, PhD. It was composed of eight internationally known experts from outside Hopkins, the scientists and ethicists of Hopkins' Program in Cell Engineering, Ethics and Public Policy and one additional Hopkins faculty member. More Info
Two-Day Grant Writing Workshop Starts Dec. 9 -- The first part of a two-day grant writing workshop to assist first-time applicants with writing a National Institutes of Health or other peer-reviewed proposal will take place Dec. 9 from 8:30 am until 4 pm. Attendees should have an application in the planning or writing stages and will choose from among three dates in mid-January for the second workshop day, which will be spent discussing their respective Abstract and Specific Aim sections. Registration is required and space is limited. Email Sabrina Welborn at jhmipdo@jhmi.edu to register and to obtain more information.
Hirschi to Present Vascular Cell Engineering Seminar Dec. 5 -- At 9 am, Friday, Dec. 5, Karen Hirschi, PhD, associate professor of pediatrics and molecular and cell biology at Baylor College of Medicine, will present "Vascular Progenitors in Adult and Embryonic Tissues" as part of the seminar series for the Johns Hopkins Institute for Cell Engineering's Program in Vascular Cell Engineering.
University-Wide Conflict of Interest Training Deadline Dec. 31 -- All University faculty, staff, researchers, students, trainees and administrators (including administrative assistants) must complete the "Conflict of Interest and Commitment" online training module by Dec. 31. The training module is at https://secure.lwservers.net .
http://www.hopkinsmedicine.org/faculty_staff/policies/facultypolicies/coi_training_module.html
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