JAX- Press Releases for The Jackson Laboratory

Jackson Laboratory receives $1.44m federal grant for Duchenne muscular dystrophy models

Thu, 11 Mar 2010 16:13:47 -0500

March 12, 2010/Bar Harbor, ME - A $1.44 million grant from the U.S. Department of Defense (DoD) to The Jackson Laboratory will expand research resources devoted to finding a cure for Duchenne muscular dystrophy (DMD) and other neuromuscular disorders, the office of U.S. Representative Mike Michaud announced.

Rep. Michaud, with support from U.S. Rep. Chellie Pingree, worked with House leadership to ensure that the funding would be included in the U.S. Defense appropriations for this year. His inspiration: Brian and Alice Denger, whose two sons have DMD. Patrick, 17, and Matthew, 15 attend Biddeford High School. The Dengers have been frequent advocates for research funding on Capitol Hill, and have visited The Jackson Laboratory, meeting with Associate Professor Greg Cox, Ph.D., who studies DMD and other neurodegenerative disorders.

Jackson researchers report new clue to normal retinal vascular development

Mon, 1 Mar 2010 15:09:17 -0500

March 2, 2010/Bar Harbor, ME - The LAMA1 gene helps to orchestrate the exquisitely intricate processes that build a healthy retina. Jackson Laboratory researchers have pinpointed a variation in the mouse version of LAMA1 that disrupts this process, causing eye abnormalities.

During normal development, a network of blood vessels grows to supply blood to the developing eye; this network recedes by the time a baby is born. Professor Patsy Nishina, Ph.D., and colleagues at French and U.S. research institutes report in the Journal of Biological Chemistry that mutations in Lama1 (the mouse version of the human gene) disrupt retinal development and can also lead to random blood vessel growth (intravitreal neovascularization) inside the eye.

According to Richard Smith, M.D., a Jackson ophthalmologist and a coauthor of the paper, "Development of the retina is highly complex, involving many different factors, any one of which can go wrong. Anything we can learn about which genes control retinal development can offer potential avenues to treat or even prevent eye diseases."

Jackson researchers find genetic links to condition that causes kidney damage in diabetics

Wed, 17 Feb 2010 14:20:30 -0500

February 18, 2009/The Jackson Laboratory - Albuminuria, or proteinuria is a condition in which urine contains an abnormal amount of the protein albumin, and is a sign of kidney damage resulting from diabetes or other medical conditions. A Jackson Laboratory research team led by Research Scientist Ron Korstanje, Ph.D., has discovered two genes that are associated with albuminuria in both aging mice and human patients with diabetic kidney disease.

A leap forward in cancer diagnostics: Gene transcript variations that signal cancer

Tue, 16 Feb 2010 16:41:49 -0500

February 17, 2010/The Jackson Laboratory - Researchers at The Jackson Laboratory have discovered telltale variations in mRNA processing -- the cell's protein-building function -- that correspond to cancer. The team showed that they could distinguish among similar tumor subtypes with at least 74 percent accuracy; the current standard in molecular diagnostics is about 10 percent.

"Microarray diagnostics have been with us for 20 years, but so far haven't lived up to their promise," Dr. Mills says. "The profiles that come off microarrays don't accurately detect most cancer cases, and even when they do, they don't categorize them correctly."

The Jackson team found that the molecular profiles, which basically indicated which genes were "on" or "off," miss an important factor: subtle differences in genes that orchestrate the processes in other genes.

Maine Ahead magazine features "Private Tour" of The Jackson Laboratory

Fri, 12 Feb 2010 11:49:22 -0500

February 12, 2010/The Jackson Laboratory - The cover story in the February-March issue of Maine Ahead magazine is a "Private Tour" feature on The Jackson Laboratory, a detailed look behind the scenes at the nonprofit biomedical research institution.

"This is not a place for pessimists," writer Henry Garfield begins the article. "Peek into any laboratory off any corridor of the Jackson Lab--also known as 'JAX'--and you will find people energetically devoting their days to finding solutions to some of our most complex medical problems."

Researchers in Japan, Bar Harbor find 25 potential leukemia targets

Fri, 12 Feb 2010 11:45:53 -0500

February 12, 2010/Bar Harbor, ME -- Researchers in Japan, in collaboration with Jackson Laboratory Professor Leonard Shultz, Ph.D., have figured out how to identify molecules that are present in leukemia stem cells but not in normal blood stem cells. The 25 molecules thus discovered are each a potential target for treating acute myeloid leukemia (AML).

The discovery may help scientists develop effective treatments for rare leukemia stem cells, which are not only resistant to chemotherapy but thought to be responsible for high rates of often fatal relapse. In the introduction to their study, published in Science Translational Medicine, the researchers note, "Despite advances in cancer therapeutics and supportive care, long-term outcomes of patients with AML remain dismal. Even after complete remission in which the whole-body leukemia burden is reduced to nearly undetectable values, most patients eventually succumb to disease relapse."

The Jackson Laboratory salutes Alan Davis

Fri, 15 Jan 2010 12:05:11 -0500

January 15, 2010/Bar Harbor, ME - Alan Davis of Walpole, Maine, was one of The Jackson Laboratory’s most dedicated and long-serving supporters. Mr. Davis was a former board member, honorary trustee, and at the time of his death, on Jan. 14, he was chair of the Maine Chapter of the National Council, the Laboratory’s volunteer organization.

Jackson Laboratory President and CEO Rick Woychik, Ph.D., said, "Alan had an intense interest in our mission and in helping us to get our message out, so that the world could better understand the Laboratory’s impact on improving health and alleviating suffering."

State energy efficiency grant of $1M awarded to The Jackson Laboratory

Fri, 8 Jan 2010 13:44:42 -0500

Bar Harbor, Maine -- The Jackson Laboratory has received a $1 million grant frhttp://www.jax.org/about/green.htmlom the Regional Greenhouse Gas Initiative, an East Coast greenhouse cap-and-trade program, to help pay for an energy-efficient heating conversion. As reported in the Bangor Daily News, the Laboratory plans to replace its oil-burning heating system with biomass burners, a $4.4 million project.

The Jackson Laboratory, a nonprofit biomedical research institution and one of Maine's largest employers, has received the Northeast Efficiency Partnership Award and is recognized as a regional energy conservation leader.

Read about green initiatives at The Jackson Laboratory

Jackson research team finds protein controlling chromosome recombination "hotspots"

Thu, 31 Dec 2009 14:00:00 -0500

December 31, 2009/Bar Harbor, ME - Jackson Laboratory scientists have found that a protein, Prdm9, turns certain locations on chromosomes into "hotspots" of recombination activity during reproduction.

Genetic recombination, in which chromosomes "cross over" and essentially exchange segments during meiosis, is a fundamental part of sexual reproduction. It ensures greater genetic diversity and helps with the separation of chromosomes to ensure that eggs and sperm have only one copy of each chromosome, instead of the pairs found in almost all other kinds of cells.

Recombination is an extraordinarily precise process. The segments exchanged have to be exactly the same length, without even one extra base, so that they don't introduce disastrous "frame-shift" mutations (like skipping a button when putting on a shirt: all the rest of the buttons will be matched with the wrong holes).

Scientists have observed so-called hotspots on chromosomes, where recombination occurs most frequently, but lacked understanding of how they develop and operate. In a paper published in Science Express (online December 31, 2009), Jackson Laboratory Professor Ken Paigen and colleagues provide some of the first insights into what regulates recombination hotspots.

Jackson aging research on Nature, Science "top 10" lists of 2009 scientific news

Wed, 23 Dec 2009 14:08:14 -0500

December 23, 2009/Bar Harbor, ME - Two of the world's most influential science journals have tapped a Jackson Laboratory research report for their year-end "top 10" lists of the most significant scientific breakthroughs for 2009, across all sciences.

In July, Jackson Laboratory Professor David Harrison and collaborators reported in the journal Nature that rapamycin, a drug used to prevent organ rejection in human transplant recipients, can significantly extend the lifespan of mice. Harrison's team fed rapamycin to mice late in their life--600 days of age--and extended their lifespan by 9 to 14 percent, making rapamycin the first pharmacological intervention proven to lengthen mammalian lifespan.

This research was included in Nature's year-end tally of the top 10 science stories most accessed by their readers. The editors of Science also selected the Jackson Laboratory report among the top 10 scientific breakthroughs of the year.

Mary Anne Handel of The Jackson Laboratory named AAAS Fellow

Thu, 17 Dec 2009 14:00:32 -0500

Washington D.C. -- Mary Ann Handel of The Jackson Laboratory has been awarded the distinction of AAAS Fellow. Election as a Fellow is an honor bestowed upon members of the American Association for the Advancement of Science by their peers.

As part of the Section on Biological Sciences, Dr. Handel was elected as an AAAS Fellow for "distinguished contributions to the understanding of mammalian gametogenesis and its genes, and service to reproductive biology research, including as Editor-in-Chief of Biology of Reproduction."

"This is a most well-deserved honor," says Jackson Laboratory President and CEO Rick Woychik, Ph.D. "Mary Ann is not only a distinguished scientist in her field of reproductive genetics, but she is also a generous mentor and collaborator."

Prize4Life and The Jackson Laboratory team up to fight ALS

Thu, 10 Dec 2009 08:56:27 -0500

December 10, 2009/The Jackson Laboratory - Prize4Life, an organization dedicated to finding a cure for amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease), is partnering with The Jackson Laboratory to help more researchers identify treatment candidates that increase the lifespan of mice that model ALS.

The Jackson Laboratory will provide the most widely used ALS mouse models, and expert guidance for how to work with them, to researchers participating in the Prize4Life $1 million challenge. Established in 2008, the Avi Kremer ALS Treatment Prize is named for a Harvard Business School student who was diagnosed with ALS and who, with fellow students, founded Prize4Life in 2004 to accelerate research for treating and curing ALS by using large inducement prizes.

Jackson researchers identify essential factors in brain organization

Tue, 1 Dec 2009 14:17:44 -0500

December 1, 2009/The Jackson Laboratory (Bar Harbor, ME) - A Jackson Laboratory research team led by Associate Professor Robert Burgess has shown that two proteins, called DSCAM and DSCAML1, are essential to the proper arrangement (what scientists call "mosaicism") of neuronal circuits in the retina. The finding could light the way to understanding a wide range of neurodevelopmental defects.

Acting as a kind of mortar in the brain mosaic, DSCAM and DSCAML1, which have already been implicated in brain development in fruit flies and birds, appear to exert just the right attractive and repulsive forces to ensure that neurons of the same type form well-defined synaptic connections.

In research published in the journal Neuron, Burgess and his colleagues show that in the absence of DSCAM, retinal neurons do form synapses, but they clump together without the regular spacing needed to ensure an absence of gaps in the brain circuitry. In other parts of the brain, such clumping could underlie a number of disorders, including Tourette's syndrome and Down syndrome--in fact, DSCAM stands for "Down syndrome cell adhesion molecule."

A commentary essay by Stanford University neurobiologist Andrew D. Huberman hails the researchers' work, noting that they provide "clear answers" to questions about the role of DSCAM "and in doing so, unveil a remarkable aspect of the adhesion code that underlies neuronal circuit wiring."

Kill the cancer, not the patient: New approach to testing chemo drugs

Thu, 19 Nov 2009 11:23:09 -0500

November 18, 2009/Bar Harbor, ME - For cancer patients on chemotherapy, the "cure" can be as deadly as the disease itself. Adverse drug reactions are one of the leading causes of death among patients receiving cancer treatment. Jackson Laboratory Professor Gary Churchill wants to change that. With a new two-year, $1 million grant from the National Cancer Institute, Churchill is launching a radical new approach to testing three chemotherapeutic drugs for potential toxic effects. Chemo drugs are supposed to be toxic--to cancer cells. But they're notorious for their unpredictable effectiveness and for causing systemic toxic reactions in patients. "Adverse drug reactions can be difficult to study in humans," Churchill says. "Every individual is genetically unique and lives in an uncontrolled environment. That's why we need animal model systems to fully understand the genetic basis of drug response." Testing chemo drugs in animal models is not new, but Churchill's approach is. Instead of working with one hybrid strain of mouse, as is the pharmaceutical industry standard, The Jackson Laboratory is developing a new mouse variety that is designed to maximize genetic diversity. Each one of these "Diversity Outbred Mice" will be genetically unique and, as a whole, the population approximates the genetic diversity observed in human populations.

$1M NIH grant funds Jackson role in biological "translation dictionary"

Thu, 19 Nov 2009 11:22:02 -0500

November 16, 2009/Bar Harbor, ME -- A $1 million federal research grant to Jackson Laboratory Associate Professor Judith Blake, Ph.D., will provide additional funding for an international project to provide structured, controlled vocabularies (ontologies) for use in biomedical research. Over the years, scientists working with various model organisms have accumulated species-specific terms for genes, proteins and other biological structures, functions and processes. Yet despite the millions of years of evolution that divide a yeast cell from a mouse, and a mouse from a human, these features are remarkably uniform across species. The Gene Ontology (GO) Consortium, based at The Jackson Laboratory, helps scientists around the world use a consistent vocabulary to communicate, integrate and interrogate their findings.

Jackson videos win awards in statewide competition

Thu, 19 Nov 2009 09:43:18 -0500

November 10, 2009/Portland, Maine - A six-minute video introducing The Jackson Laboratory and an eight-minute video describing the Laboratory's role in personalized medicine have won Broderson Awards from the Advertising Club of Maine.

The videos received Silver Awards in the long-form marketing video category. The awards were announced Oct. 21 at a banquet in Portland hosted by former Maine Gov. Angus King and Adweek critic Barbara Lippert. Both videos were produced by AirStream Pictures of Gorham, Maine, in partnership with the Laboratory. David Fuller, owner of AirStream, directed the productions and accepted the awards. Chuck Griffith of Pound Ridge, N.Y., was creative director for the introductory video.

Watch the introductory video (6:19)

Watch the personalized medicine video (8:07)

Jackson Laboratory considering new facility

Wed, 14 Oct 2009 08:29:53 -0400

October 14, 2009/The Jackson Laboratory - The Jackson Laboratory is evaluating the feasibility of establishing an institute for personalized medicine. The institute would more directly apply the Laboratory's expertise in genomics and bioinformatics to problems of human health and disease.

Drastic reductions in the cost and speed of whole-genome sequencing and a deeper understanding of genetic networks are opening up exciting new possibilities for treating patients based on their unique genetic makeup, said Jackson President and CEO Rick Woychik, Ph.D.

"We are on the verge of a whole new era in medicine, and we expect to play a pioneering role in the science that will accelerate personalized medicine," Woychik said. "Understanding the complex genetics of disease and of the individual will enable physicians to treat patients more effectively, reduce drug side effects, and lower the cost of health care."

$2.4M NIH grant to The Jackson Laboratory for "FaceBase" project

Tue, 6 Oct 2009 08:29:13 -0400

October 6, 2009/National Institutes of Health, NIDCR - Jackson Laboratory researchers including Professor Leah Rae Donahue, Ph.D., and Research Scientist Stephen Murray, Ph.D., are part of a new, multi-institutional National Institutes of Health initiative to understand craniofacial birth defects.

The 5-year, $2,352,385 grant to The Jackson Laboratory is one of 11 research and technology grants of the new FaceBase Consortium funded by the National Institute of Dental and Craniofacial Research (NIDCR). The initiative will systematically compile the biological instructions to construct the middle region of the human face and precisely define the genetics underlying its common developmental disorders, such as cleft lip and palate. The mid-face includes the nose, upper lip, and the palate, or roof of the mouth.

Third JAX Summer Student wins Nobel Prize

Tue, 6 Oct 2009 09:43:10 -0400

October 5, 2009/Bar Harbor, ME - An alumnus of The Jackson Laboratory’s historic Summer Student Program is a winner of the 2009 Nobel Prize in Physiology or Medicine. Jack W. Szostak, Ph.D., is the third Summer Student Program alumnus to win the Nobel Prize, after Laureates David Baltimore and Howard Temin, who were both at the Laboratory in 1955.

Today a professor at Harvard Medical School and Massachusetts General Hospital in Boston, and a Howard Hughes Medical Investigator, Dr. Szostak spent the summer of 1970 at The Jackson Laboratory, while an undergraduate at McGill University, studying genes associated with thyroid function under the mentorship of Dr. Chen K. Chai.

Dr. Szostak shares this year’s Nobel Prize with Drs. Elizabeth H. Blackburn and Carol W. Greider "for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase." Telomeres, structures on the ends of chromosomes, appear to have an important role in preventing damage to DNA during cell division. Their function, or failure to function, is implicated in aging, cancer and other diseases.

In newly patented process, The Jackson Laboratory "freezes" genetic variation in mice

Tue, 22 Sep 2009 13:10:36 -0400

September 22, 2009/Bar Harbor, Maine - Today the U.S. Patent and Trademark Office has awarded The Jackson Laboratory a patent for a process that effectively prevents random change or "genetic drift" in its inbred mouse colonies.

Thanks to the close match between human and mouse genes, researchers around the world use mouse models to study human biology and diseases. Today more than 4,000 mouse models are available from The Jackson Laboratory, each with a very specific genetic profile.

However, just a few of these models -- standard inbred strains -- represent the vast majority of mice used in research and are consequently bred in large numbers. Because "evolution happens" even among genetically identical animals, there's always the chance of random new mutations arising over time or place in these mouse colonies, potentially introducing unknown variables into researchers' experiments.

$2.1M NIH construction grant will support Jackson research expansion

Wed, 16 Sep 2009 16:22:24 -0400

Bar Harbor, Maine -- A new $2.1 million National Institutes of Health grant to The Jackson Laboratory will fund construction of space for the institution’s expanding bioinformatics and computational biology programs.

Jackson Laboratory bioinformatics and computational biology scientists develop the ever-growing quantity of genetic data into sophisticated tools, available to the worldwide research community, for understanding gene function. To meet the rapidly expanding demand for these data and tools, the Laboratory is recruiting four new faculty members over the next five years with expertise in applying computational approaches to solving biological problems.

Nature opinion: Jackson Laboratory represents best practices in sharing research materials

Thu, 10 Sep 2009 11:51:18 -0400

September 10, 2009/Nature Online - Sharing knowledge is essential for the progress of science, but researchers don't always release data and research materials, even after publication of work. In May, representatives of biomedical research institutions, funding agencies and journals from around the world gathered in Rome to tackle the barriers to more effective sharing of data and research resources, particularly mouse strains and embryonic stem cells.

These representatives, including David Einhorn, house counsel of The Jackson Laboratory, have published an opinion article in the top journal Nature, setting out an agenda for the worldwide scientific community to follow. The Jackson Laboratory's commitment to distributing research resources to the worldwide scientific community was cited as "an example of good practice" of sharing resources.

Bangor Walk raises funds for ALS research

Mon, 31 Aug 2009 15:56:22 -0400

August 31, 2009/Bangor, Maine -- At least 200 ALS patients and their families, friends and supporters braved the rain in Bangor's Hayford Park on the morning of Saturday, August 29, for the second annual Walk to Defeat ALS. The fundraising event was sponsored by the ALS Association.

Jackson Laboratory Associate Professor Greg Cox, Ph.D., keynote speaker of the event and an ALS Association grantee, came with members of his laboratory and family. He said, "Events such as the Walk to Defeat ALS help to raise awareness about the need for continued clinical and basic research on ALS. My laboratory is taking advantage of the power of mouse genetics to identify factors that can alter the onset or progression of ALS. We hope to use this knowledge to identify new targets for therapeutic development."

Also attending the event were Nancy Venner, director of community services for the ALS Association, and two patient services coordinators from the association's Northern New England Chapter, Christine Richards of New Hampshire and Nell Davies of Maine.

New researcher, trustees, awards announced

Tue, 18 Aug 2009 11:31:06 -0400

August 18, 2009/Bar Harbor, ME - ackson Laboratory Trustee Sam Little (top), grandson of Jackson founder C.C. Little, is the new president of the institution’s support group, The National Council. Two new Trustees and other appointments were also announced at the Laboratory’s 80th Annual Meeting and Discovery Day in Bar Harbor on August 14-15.

The Laboratory confirmed Stewart Hen and Kathleen Corbet to the Board of Trustees. Brian Wruble (bottom) was reelected as chairman of the Board, and long-serving Board members Bill Rudolf and Harry Sears, M.D., became Trustees Emeriti. Robert B. Darnell, M.D., Ph.D., Robert and Harriet Heilbrunn Professor in Cancer Biology at Rockefeller University in New York and Howard Hughes Medical Investigator, joined the Laboratory's Board of Scientific Overseers.

At the annual National Council Discovery Day on Saturday, the group met and shared a day of presentations and tours with employees and members of the local community. Harry Lodge, M.D., coauthor of the popular Younger Next Year series of books, gave a talk and led a panel discussion, followed by a presentation by Jackson Laboratory Professor David Harrison, Ph.D.

Retired Jackson scientist funds two new $100k endowments

Mon, 17 Aug 2009 11:28:25 -0400

August 17, 2009/Bar Harbor, ME - Jackson Laboratory Professor Emeritus Douglas Coleman, Ph.D., winner of the 2009 Shaw Prize in Life Science and Medicine, has established two $100,000 endowments with his Prize earnings to support research and education at the Laboratory.

The Douglas Colelman Research Fund will support investigators, with preference given to early-career scientists at The Jackson Laboratory who are studying obesity and diabetes, the fields in which Dr. Coleman is recognized as a pioneer.

Jackson researchers build a better mouse (gene) trap

Sun, 9 Aug 2009 11:56:10 -0400

August 9, 2009/Bar Harbor, ME - To fully explore complex genomic and genetic questions, researchers need better tools. A new microarray developed by scientists at The Jackson Laboratory and University of North Carolina can capture the full spectrum of genetic diversity in laboratory mice, enabling the kind of genome-wide association studies in mice that have been successful in human populations.

The JAX® Mouse Diversity Genotyping Array, designed by Jackson Laboratory Professor Gary Churchill, Ph.D., and Fernando Pardo Manuel de Villena, Ph.D., of the University of North Carolina, provides an efficient and powerful platform for characterizing mice and gaining insight into a variety of genomic inquiries.

Groundbreaking on new importation facility marks turning point for (Lab's) economy

Wed, 5 Aug 2009 12:11:19 -0400

August 5, 2009/Bar Harbor, ME - Citing figures they say demonstrate that The Jackson Laboratory is emerging from last year’s economic slump, lab officials ceremonially broke ground Wednesday on a new facility expected to help the lab expand one of its more profitable products.

The importation isolation building, which is being funded in part by a $4.7 million grant from the taxpayer-supported Maine Technology Asset Fund, would provide space for many of the lab’s reproductive services functions. The MTAF grant is paying for half of the building’s construction and the lab is funding the rest, lab officials said.

UMaine network aims to speed research links

Tue, 21 Jul 2009 12:06:00 -0400

July 21, 2009/Orono, ME - In U.S. history, May 10, 1869, is notable because it was the day a golden spike was driven into the ground in Utah to indicate the final step in the connection of the country’s first transcontinental railroad.

What happened Monday in Salem, N.H., may not have the same national historic implications, but it represented a huge step forward for research facilities, universities and colleges in Maine, Massachusetts, New Hampshire, and possibly beyond.

At about 3 p.m. Monday, a fiber-optic line from Cambridge, Mass., was spliced with a line from Durham, N.H., forming a connection with the Maine Research and Education Network, or MaineREN, whose northern end points are The Jackson Laboratory and MDI Biological Laboratory in Bar Harbor and the University of Maine in Orono.

Jackson researchers net nearly $461k in new research grants

Thu, 16 Jul 2009 10:35:59 -0400

July 16, 2009/Bar Harbor, ME - Three Jackson Laboratory researchers were awarded new grants from the National Institutes of Health. The awards are part of the federal governments economic stimulus initiative known as the American Recovery and Reinvestment Act of 2009 (ARRA).

Jackson Lab team extends lifespan of mice with transplant drug

Wed, 8 Jul 2009 14:44:56 -0400

July 8, 2009/Bar Harbor, ME - A drug used by human transplant recipients to prevent rejecting their new organ can significantly extend the lifespan of mice, finds a paper published online this week in Nature.

Rapamycin is a bacterial product originally found in a soil sample from Rapa Nui, or Easter Island. It targets TOR, a kinase that regulates protein translation, cell growth and cell metabolism in response to environmental cues. Reducing TOR function has already been shown to extend the life of yeast, nematode worms and flies, but now Jackson Laboratory Professor David Harrison and colleagues report the effect for the first time in mammals.

The team fed rapamycin to mice late in their life - 600 days of age - and showed that the median and maximal lifespan of treated animals was extended by 9-14%. Currently, the only way to extend the life of a rodent is by severely restricting its diet, so this marks the first report of a pharmacological intervention that lengthens the life of mammals.

California research agency grants $3.4M to The Jackson Laboratory--West

Mon, 22 Jun 2009 12:43:47 -0400

June 22, 2009/Sacramento - The Jackson Laboratory has received a $3.4 million grant from the California Institute for Regenerative Medicine (CIRM), the state's stem cell agency, to help speed the development of new therapies for cancer, Alzheimer's, Parkinson's and other diseases.

A nonprofit biomedical research institution based in Bar Harbor, Maine, The Jackson Laboratory's facility in Sacramento provides research services to the West Coast biomedical community. The Jackson Laboratory--West will use the CIRM grant to develop new mouse models of human disease that can be used to test innovative stem cell treatments.

Jackson Laboratory scientist wins Shaw Prize, "Nobel of the East"

Tue, 16 Jun 2009 16:27:49 -0400

June 16, 2009/The Jackson Laboratory - Jackson Laboratory Professor Emeritus Douglas Coleman, Ph.D., a pioneer in obesity and diabetes research, will share the prestigious Shaw Prize in Life Science and Medicine with Dr. Jeffrey Friedman of Rockefeller University and the Howard Hughes Medical Institute. The prize, issued by the Shaw Prize Foundation of Hong Kong, is widely regarded as the "Nobel of the East" and carries a $1 million award.

In the 1970s, Dr. Coleman conducted a series of experiments that led him to propose the existence of a "satiety factor" that would account for obesity and type 2 diabetes among certain mice. Dr. Friedman would later identify that factor as leptin, a hormone that regulates food intake and body weight. The scientists' work showed that chemical and genetic factors--not just willpower and eating habits--are involved in obesity, opening possibilities for future pharmaceutical treatments.

Jackson receives $2.1M in Maine Technology Asset Fund award

Mon, 15 Jun 2009 10:40:25 -0400

June 9, 2009/The Jackson Laboratory - The Jackson Laboratory has received a $2.1 million grant from the State of Maine to expand research space for laboratory mice and to purchase cutting-edge equipment for genetic analyses. The Maine Technology Institute (MTI) awarded the grant through the Maine Technology Asset Fund.

"This funding is a smart state investment in science, medicine and economic development, and we’re going to put it to good use," said Jackson Laboratory President and CEO Rick Woychik, Ph.D. "It will expand the Laboratory’s capacity to conduct research and development, leading to new product and service offerings for personalized medicine research, in partnership with Maine companies and nonprofit institutions."

Lethal cancer knocked down by one-two drug punch

Mon, 8 Jun 2009 10:46:37 -0400

June 8, 2009/Bar Harbor, ME - In the battle against cancer, allies can come from unexpected sources. Research at The Jackson Laboratory has yielded a new approach to treating leukemia, one that targets leukemia-proliferating cells with drugs that are already on the market.

Jackson Adjunct Professor Shaoguang Li, M.D., Ph.D., who now has a laboratory at the University of Massachusetts Medical School in Worcester, led a research team that identified a gene involved with the inflammatory response that could hold the key to treating or even preventing chronic myeloid leukemia (CML), a lethal cancer.

The gene, Alox5, processes essential fatty acids into leukotrienes, which are important agents in the inflammatory response. But according to the researchers, Alox5 has a more sinister side. It is vital to the development and maintenance of cancer stem cells.

Cancer stem cells are slow-dividing cells that are thought to give rise to a variety of cancers, including leukemia, and to be critical for maintaining them. Researchers theorize that cancer stem cells must be targeted for effective treatment of many cancers, but direct evidence is still lacking.

Maine Governor Baldacci presents Maine Fitness Award to Jackson Laboratory

Thu, 21 May 2009 21:14:02 -0400

May 20, 2009/The Jackson Laboratory - Maine Governor John Baldacci presented the Maine Fitness Award to the Laboratory in the Healthy Workplace -- Large Employer category at a ceremony in Augusta.

The Maine Fitness Awards, presented by the Governor's Council on Physical Activity, recognize people and programs that promote physical fitness and sports programs in eight different categories including youth-based, community and workplace.

Jackson & NC scientists develop genetic toxicity identifiers for drugs like acetaminophen

Tue, 5 May 2009 12:59:46 -0400

May 4, 2009/The Jackson Laboratory -Adverse reactions to medications represent one of the leading causes of death in the United States. But there may be a way to predict who is most likely to suffer a toxic side effect to a drug before it's prescribed.

In a study published online May 4 in the journal Genome Research, scientists at The Jackson Laboratory in Bar Harbor, Maine, the University of North Carolina at Chapel Hill, and other institutions report a new approach to testing drugs for potential toxicity, one that could someday result in more people benefiting from existing drugs.

See Dr. Paigen discuss his findings in this informal, 6-minute video

The Jackson Laboratory--West moves to larger Sacramento site

Mon, 27 Apr 2009 10:32:34 -0400

Sacramento, CA - The Jackson Laboratory has expanded its footprint in California, home to the world's greatest concentration of biomedical researchers. The newly renovated, 85,000-square-foot facility in Sacramento is twice the size of Jackson's previous space in West Sacramento.

According to Jackson President and CEO Rick Woychik, Ph.D., about twice as much biomedical research is conducted in California than in the entire East Coast corridor between Maine and the Research Triangle area of North Carolina. "The West Coast biomedical research community is an exciting community, and we're becoming a bigger part of it," Dr. Woychik says. "This means The Jackson Laboratory, and Maine, will benefit from a tremendous income opportunity for many years to come."

Jackson Laboratory committed to healthy environment as well as human health

Mon, 6 Apr 2009 09:18:37 -0400

Bar Harbor, Maine - Mainers know The Jackson Laboratory as a nonprofit research institution that is leading the search for tomorrow's cures. They can also be proud of the fact that the Laboratory -- one of the state's largest employers -- is also in the vanguard of institutional environmental initiatives. Ongoing efforts to reduce energy use earned The Jackson Laboratory the Northeast Energy Efficiency Partnership Award in 2006 for energy conservation leadership. According to Jackson Vice President and Chief Operating Officer Chuck Hewett, Ph.D., "The Laboratory makes it a practice to choose the most environmentally friendly materials, services and utilities available, which nowadays also often equates to lower operational costs."

The Jackson Laboratory settles with the EPA after successfully resolving compliance issues

Fri, 3 Apr 2009 09:06:36 -0400

The Jackson Laboratory has reached an agreement with the U.S. Environmental Protection Agency to pay fines associated with a November 2006 inspection. The Laboratory quickly addressed the issues identified during that inspection, most of which involved minor record-keeping, and none of which represented any real threat to the environment or public safety. The Laboratory provided data that conclusively demonstrated that chemicals stored on its site did not pose a risk of explosion as originally alleged by the EPA.

The Jackson Laboratory considers environmental health and safety to be of the utmost importance. We are pleased that we have been able to resolve these issues with the EPA.

The fines of $161,680 were reduced from the $213,670 originally proposed by the EPA.

Rick Woychik: Jackson vital to Maine's health & economy

Sat, 28 Mar 2009 13:43:49 -0400

The Jackson Laboratory is vital to Maine's economy and the future health of Mainers, says Jackson President and CEO Rick Woychik, Ph.D.

In an op-ed column in the March 28-29 edition of the Bangor Daily News, Dr. Woychik notes that "while Maine's economy, like the world economy, has slowed, the ravages of disease have not."

Board member makes $1 million challenge gift to The Jackson Laboratory

Mon, 23 Mar 2009 19:37:31 -0400

Bar Harbor, Maine - Geneticist and author Weslie Janeway of New York has made a $1 million "challenge gift" to The Jackson Laboratory for the recruitment and support of new scientists working to understand the genetic basis of human disease. The challenge gift, intended to encourage $1 million in matching gifts from other donors, will be used to pay for faculty starting salaries, lab equipment and experiments.

"Mrs. Janeway’s generous gift will help us attract bright young faculty with new ideas and approaches to enhance our genetics research at the Laboratory," said Rick Woychik, Ph.D., president and CEO of the Laboratory. "A secure funding base is necessary to attract outstanding researchers," Mrs. Janeway said. "This represents the best possible investment in the future of The Jackson Laboratory and its work in the basic science that makes it possible to advance human health."

The gift is timely because the Laboratory has developed a five-year strategic plan to expand its faculty to 45 principal investigators from the current 38 by 2014.

Jackson awarded $12,500 MTI grant to commercialize new stem cell technologies

Fri, 13 Mar 2009 11:22:22 -0400

The Maine Technology Institute has awarded a Jackson Laboratory team a $12,500 seed grant to investigate new stem cell technologies that could advance the future of individualized medicine.

Embryonic stem (ES) cells have the capacity to grow into any kind of cell in the body: heart, lung, pancreas, liver, etc., and thus hold promise for repairing or even reconstructing organs damaged by diabetes, cancer or other diseases. However, there's a built-in problem: Tissues created from any source besides the patient's own cells could be rejected by the patient's body, yet the patient's own ES cells are not available because they are present only in very early human embryos.

Enter new technologies for converting adult cells of the body into embryonic-like stem cells by adding a combination of reprogramming factors. Under the MTI grant, the Jackson researchers will conduct a study of whether these so-called induced pluripotent stem (iPS) cells do indeed function as ES cells would.

Jackson director, scientist to speak April 30 at Rockport Opera House

Fri, 13 Mar 2009 11:21:53 -0400

Dr. Rick Woychik, president and CEO of The Jackson Laboratory in Bar Harbor, Maine, and Jackson cancer researcher Dr. Kyuson Yun, are speaking Thursday, April 30 at 7 p.m. at the Rockport Opera House in Rockport, Maine. Part of the Rockport Public Library's "Spring Into Health" series to educate the public about important medical issues, the talk is fre and open to the public.

Laboratory reduces workforce to weather recession

Fri, 6 Mar 2009 12:46:37 -0400

The deteriorating conditions in the world economy will force The Jackson Laboratory to reduce its workforce by about 55 people and temporarily curtail the workweek to 37.5 hours for about 315 of its hourly employees.

These actions, announced to Laboratory staff on Thursday, follow a careful, six-week assessment of the Laboratory's financial situation by senior managers and are part of a wide-ranging plan to cut operating costs and boost revenues. A hiring freeze implemented in January also remains in effect except for positions funded by external grants and a few select positions deemed mission critical.

Jackson director to speak March 22 in Boca Raton, Fla.

Fri, 27 Feb 2009 12:44:56 -0400

Dr. Rick Woychik will address the future of individualized medicine, explaining how scientists are working toward a new kind of medicine, in which treatments are tailored to each patient's personal genetic profile.

Hosted by Sue Goldman, president of the board of Congregation B’nai Israel, and her husband Dr. Howard Goldman, Dr. Woychik will share his presentation on Sunday, March 22 at Congregation B’nai Israel, 2200 Yamato Road, Boca Raton, Fla., at 6:30 p.m., following a 6:00 p.m. reception.

Jackson ranks #2 among nation's "Best Places to Work" for postdocs

Tue, 24 Feb 2009 15:33:06 -0500

The Jackson Laboratory ranks among the nation's top institutions for scientists in the postdoctoral phase of their career--also known as "postdocs". The Laboratory was voted #2 in a poll of postdocs conducted by The Scientist, a magazine for people working in the life sciences, up from the #9 spot in 2008.

The Scientist: Jackson established mouse genetics, cancer researchers' careers

Wed, 18 Feb 2009 10:47:41 -0500

The current edition of the life sciences magazine The Scientist includes two articles noting The Jackson Laboratory's central role in modern biomedical research.

In "Fancy This," reporter Andrea Gawrylewski traced the earliest research colonies of genetically defined mice, established by Jackson Laboratory founder Clarence Cook Little, to a Massachusetts breeder of pet "fancy mice," Abbie Lathrop. "Mapping with Mice" is a profile of the prominent husband-and-wife cancer research team of Nancy Jenkins and Neal Copeland, who spent an important phase of their career conducting research at The Jackson Laboratory.

Study: Calorie restriction helps only obese mice live longer

Wed, 18 Feb 2009 10:32:50 -0500

Does a calorie-restricted diet actually lengthen your life? Probably not unless you're already overweight, say scientists at the University of Southern California and North Texas Health Science Center.

The scientists studied two strains of JAX® Mice from The Jackson Laboratory to see whether subjecting them to a low-calorie diet prolonged their lifespan by lowering the rate of metabolism. The C57BL/6J mouse tends to gain weight throughout its lifetime, while the DBA/2J mouse stays lean.

Do-it-yourself sperm cryo kit launched by The Jackson Laboratory

Tue, 10 Feb 2009 10:22:51 -0500

Critical technology for preserving and recovering mouse strains took a giant leap forward this week - out of the laboratory and into the hands of researchers - as The Jackson Laboratory (JAX) introduced the first "do-it-yourself" Sperm Cryopreservation Kit for mice.

Containing all the materials and instructions necessary for the preservation of three, six or nine strains of mice, the new JAX® Sperm Cryopreservation Kit translates cutting-edge technology into an easy-to-use product, while providing the assurance that comes from robust quality control, testing, and long-term storage at The Jackson Laboratory.

For the first time, researchers can cost-effectively cryopreserve novel mouse strains in their own laboratories - without worrying about shipping live mice or whether or not cryopreservation was successful, and without the cost and infrastructure necessary for long-term storage. The Kit includes both quality control testing to assess fertilization capacity and three years of storage in liquid nitrogen (in three separate tanks, in two locations) at JAX as part of the purchase price. The Kit is designed for strains that can be recovered on the following inbred and genetic backgrounds: C57BL6/J, DBA/2J, C3H/HeJ, FVB/NJ, B6129SF1/J.

How Jackson Laboratory founder C.C. Little revolutionized biomedical research

Fri, 30 Jan 2009 11:15:27 -0500

In 1909, while still an undergraduate at Harvard University, Clarence Cook Little started to develop the first inbred strain of laboratory mouse.

In the January edition of New Scientist magazine, writer Sharon Oosthoek relates how Little, who would found The Jackson Laboratory in 1929, revolutionized the progress of biomedical research for the last 100 years.

The article is available to New Scientist subscribers online and is also on the ABC news website.

Blocked protein prevents Lupus in mouse model

Fri, 30 Jan 2009 11:12:09 -0500

Mice from a strain that ordinarily develops systemic lupus erythematosus (SLE), but bred with a deficiency in receptor for the protein Interleukin 21, stayed healthy and exhibited none of the symptoms of the disease, researchers at The Jackson Laboratory and National Institutes of Health report.

SLE is an autoimmune disease, with symptoms of varying severity including include painful or swollen joints, unexplained fever and extreme fatigue. An estimated 2 million Americans --nine out of 10 of them female -- live with SLE.

The primary job of the immune system is to identify and vanquish potentially dangerous infectious pathogens. Autoimmune diseases develop when immune system instead unleashes this potent defense system against the individual's own tissues, with predictably severe consequences.

Unlike other autoimmune diseases such as Type 1 diabetes, in which the immune response is focused on certain tissues, SLE is a systemic disease in which abnormal antibodies are produced that injure a variety of tissues and organs, including the skin, heart, lungs and kidneys.

The cause of SLE is not well understood, but recent work by a Jackson Laboratory research team led by Professor Derry Roopenian is shedding light on how the disease develops and offers hope for better therapies.

Mutant mice funded for 50 years at Jackson

Tue, 20 Jan 2009 09:13:06 -0500

January 2009 marks 50 years of federal funding for the world's largest collection of mice with naturally occurring, or spontaneous, mutations. These mice have helped researchers around the world study some of humanity's toughest diseases.

Why Jackson's collection is special
The Jackson Laboratory is recognized throughout the scientific world as the institution that made the laboratory mouse the premier model for the study of basic biology and genetic diseases. By carefully inbreeding mice so that each colony is, for all intents, a large family of genetically identical "twins", JAX® Mice are consistent, standardized research models. As part of Jackson's program to maintain this genetic consistency, animal care technicians are trained to identify mouse offspring that look or act differently from their parents -- the first sign that a spontaneous mutation may have occurred.

What's so special about mutant mice?
Mice and humans share the vast majority of their genes, and mice get the same diseases as humans, for the same genetic reasons. Since the 1980s, with the advent of gene transfer technology, it has been possible to insert or delete genes to create a new mouse model for a given disease, based on what is known about the genetics of that disease.

However, given the complexity of diseases like cancer, diabetes and heart disease, which may involve the interaction of dozens or even hundreds of genes, many scientists believe that diseases are best modeled when they occur naturally, as they do in the human population.

"Spontaneous mutations provide gene discovery in its most basic form," says Dr. Leah Rae Donahue, Jackson's director of genetic resource sciences. "In mice with a spontaneous mutation, you notice the clinical 'symptoms' of a disease first, and when you investigate the genetics you may discover a gene that no one suspected was involved in the disease."

New clues emerge as to how gene activity affects aging

Mon, 29 Dec 2008 12:00:02 -0500

New evidence may explain why it is that we lose not only our youthful looks, but also our youthful pattern of gene activity with age. A report in the journal Cell by researchers at Harvard Medical School, The Jackson Laboratory and other institutions reveals that a protein perhaps best known for its role in the life-extending benefits of a low-calorie diet also maintains the stability of the mammalian genome--the complete set of genetic instructions "written" in DNA.

Jackson Laboratory in international mouse genome project

Thu, 18 Dec 2008 17:12:02 -0500

The U.K.-based Medical Research Council and Juvenile Diabetes Research Foundation have launched a $4.4 million project, involving The Jackson Laboratory and research institutions in the U.K. and Europe, to sequence the genomes of the 17 most widely used strains of laboratory mouse.

The three-year project will use next-generation sequencing technologies to produce detailed sequences for each of the strains. The DNA sequences will help to identify and characterize many human disease-related genes, and will be made openly available to the research community.

Dr. David Adams, investigator at the Wellcome Trust Sanger Institute, who will lead the project, says: "This award is a great boost for researchers around the world working to understand the genetic components of disease. We have already carried out pilot studies to guide our approach and can now move forward swiftly to deliver these new resources."

More than 400 genetically defined strains are available to the worldwide scientific community from The Jackson Laboratory and other sources, but the vast majority of researchers study a much smaller subset of 17 strains.

Jackson Trustee David Baltimore on "America's Best Leaders" list

Tue, 2 Dec 2008 13:05:46 -0500

David Baltimore's influence on science has stretched far beyond the Nobel he won at age 37 for his work on retroviruses. An early advocate for federal research on AIDS, he served as president of Rockefeller University and the California Institute of Technology, all while continuing to do research.

Jackson's Simon John named team leader in new research program

Fri, 21 Nov 2008 15:07:22 -0500

As part of a new, $40 million initiative to spark innovation and collaboration in biomedical research, the Howard Hughes Medical Institute (HHMI) has named Jackson Professor Simon John to lead one of eight teams of scientists. Dr. John is one of the nation's leading researchers in the study of glaucoma. According to HHMI, the Collaborative Innovation Awards were designed to enable the teams "to devote substantial time and energy to pursuing collaborative, transformative research." In Dr. John's case, he will be teaming with engineers at Purdue University to develop new, wireless sensor technology to monitor the intraocular pressure of a mouse eye. If successful, the technology could have a wide range of applications in human medicine, such as monitoring blood pressure around the clock. In glaucoma, the nerve cells, or neurons, that connect the eye to the brain lose function and die. These nerve cells are known as retinal ganglion cells. Since retinal ganglion cell axons -- similar to electrical wires -- travel through the optic nerve and connect the retinal ganglion cells to the brain, glaucoma is also characterized by degeneration of the optic nerve. Most currently available treatments for glaucoma focus on reducing harmfully high pressure inside the eye (known as intraocular pressure), one of the strongest known contributing factors to glaucoma. The ability to closely monitor the pressure is an important step in fully understanding the disease and how it progresses to damage neurons.

Jackson Laboratory high school mentorships featured

Fri, 21 Nov 2008 14:59:36 -0500

HHMI Bulletin: Jackson program "grandaddy of training grounds"

In just seven weeks at The Jackson Laboratory in Bar Harbor, Maine, two teenagers have become an integral part of a lab team. Bob Braun, who recently joined Jackson Lab as associate director and chair of research, is hosting high school students for the first time. He is surprised at how much valuable science these high school students have done, going beyond his carefully outlined plan for their summer. "These students have really galvanized my lab, and the lab has embraced them," he says.

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Cancer researcher joining Jackson research staff

Mon, 17 Nov 2008 09:44:42 -0500

Cancer researcher Chengkai Dai, M.D., Ph.D., will join The Jackson Laboratory faculty at the end of 2008. Dr. Dai is finishing a postdoctoral appointment at the Whitehead Institute for Biomedical Research, an independent institution affiliated with MIT. Dr. Dai studies a family of proteins, called heat shock proteins, that normally protect healthy cells from environmental stress. In cancer, however, the proteins change allegiance and instead help to protect cancer cells, allowing them to grow and divide very rapidly. Dr. Dai earned his M.D. from Tianjin Medical University in 1995, followed by an M.S. degree in 1998. He conducted graduate work with Eric Holland, M.D., Ph.D., and received his Ph.D. from the University of Texas—Houston Health Science Center in 2003. At the Whitehead Institute, his postdoctoral fellowship is in the laboratory of Susan Lindquist, Ph.D. Dr. Dai has co-authored 17 research and review articles (seven as first author) in peer-reviewed journals including Cell and Genes & Development. He received The Children's Tumor Foundation Young Investigator Award in 2006.

Scientists rank Jackson in top 20 U.S. "Best Places to Work in Academia"

Fri, 7 Nov 2008 11:21:20 -0500

The Jackson Laboratory was voted among the top 20 "Best Places to Work in Academia" in the United States for 2008. The poll was conducted by The Scientist, a magazine for people working in the life sciences. Readers participating in the survey cited job satisfaction and pay as The Jackson Laboratory's greatest workplace strengths. The Laboratory was ranked number 19 among U.S. academic research institutions. The results of the survey are published in the November edition of The Scientist.

Princeton computer scientist joining Jackson research staff in January

Tue, 28 Oct 2008 13:47:39 -0400

Computer scientist Matthew Hibbs, Ph.D., will be joining The Jackson Laboratory’s research faculty in January 2009. Dr. Hibbs received his Ph.D. from Princeton University and comes to the Laboratory after serving as a postdoctoral research assistant there.

A specialist in bioinformatics and computational biology, Dr. Hibbs began his undergraduate studies at the University of Texas interested in computer graphics, not genetics. But an early seminar in bioinformatics changed his thinking for good, and computer animation’s loss was computational biology’s gain.

Jackson Laboratory in top 20 of "Maine 100" listing

Thu, 16 Oct 2008 14:38:36 -0400

The Jackson Laboratory ranks 19th in "The Maine 100," Portland Magazine's annual listing of the top firms headquartered in Maine.

Jackson Laboratory Professor Ken Paigen receives Fulbright Senior Specialists Award

Thu, 16 Oct 2008 14:35:47 -0400

Kenneth Paigen, Ph.D., professor and executive research fellow at The Jackson Laboratory, has been selected for a Fulbright Senior Specialists project in France at Pasteur Institute during November 2008.

Statement from The Jackson Laboratory in response to EPA news release

Fri, 3 Oct 2008 09:49:03 -0400

We are concerned that the EPA would issue a news release with a list of allegations stemming from an inspection that occurred two years ago. The Jackson Laboratory operates at the highest safety standards, including its handling of the small amounts of hazardous materials and waste present on our campus.

Jackson NY Gala raises $1.3M, brings out stars

Mon, 22 Sep 2008 13:38:41 -0400

Stars of Hollywood, music and the science world came together at The Jackson Laboratory's spectacular National Gala at New York's Pierre Hotel on Sept. 18.

"Friendly" bacteria protect from diabetes

Sun, 21 Sep 2008 13:38:42 -0400

Friendly" bacteria help to stop the development of type 1 diabetes in mice, according to research conducted in part at The Jackson Laboratory and published online in Nature. The findings could one day be used to develop bacteria-based treatments for patients, say the authors.

Jackson Laboratory NY gala Sept. 18 to honor Nobel laureate, biotech investor

Tue, 16 Sep 2008 14:16:52 -0400

Nobel laureate David Baltimore, Ph.D., and renowned biotech investor Anthony B. Evnin, Ph.D., will receive Lifetime Achievement Awards at the gala, hosted by the National Council, a network of volunteers and donors who support The Jackson Laboratory.

Federal research grants totaling $4.9 million awarded for Jackson research

Mon, 8 Sep 2008 13:38:43 -0400

The National Institutes of Health announced grants totaling close to $5 million to two Jackson Laboratory scientists who study retinal diseases and embryonic development, respectively.

Nobel laureate, two investment executives join Jackson Board of Trustees

Tue, 2 Sep 2008 14:02:05 -0400

Nobel laureate David Baltimore, Ph.D., and investment executives Marie Langlois, M.B.A., and Thomas Volpe, M.B.A., M.Sc., have joined The Jackson Laboratory’s Board of Trustees. The nonprofit research institution announced these and other board changes at its August 2008 annual meeting.