SCIENTISTS UNCOVER NEW PROCESS REGULATING ELECTRICAL FIRING PROPERTIES OF NEURONS
Neurons in the brain communicate with each other using a combination of carefully regulated chemical and electrical signals. NIH Director’s Pioneer Award recipient Dr. James Eberwine and colleagues at the University of Pennsylvania and Sequenom, Inc. have discovered a novel method by which neurons selectively express proteins that control their electrical properties , reported in the December 7, 2010 issue of the Proceedings of the National Academy of Sciences. In neurons, electrical signals are controlled by channel proteins that create a pore in the cell membrane to allow positively or negatively charged ions to flow in and out of the cell. One of these channel proteins, called BKCa, helps regulate electrical signals in the hippocampus, an area of the brain that is important for learning and memory. Interestingly, the hippocampus is also the focus of many epileptic seizures, which result from disturbances in the electrical firing of neurons. The BKCa channel protein has several different variations. These protein variations arise during a cellular process called “splicing,” which is analogous to the process of cutting an undesired segment out of an audiotape and joining the resulting ends together. To make a protein, a cell must identify the piece of DNA that contains the instructions for the protein (called a gene), copy the DNA into another form of genetic material, called RNA, and then use the information encoded in the RNA to make the protein. Often, the instructions in the DNA for making a protein are not in a continuous stretch, but contain intervening sequences or “introns.” After the DNA is copied into RNA, these introns are removed and the flanking coding sequences, or “exons,” are connected to each other. It is the sequence of merged exons that tells the cell how to make a protein. Since the RNA can be spliced in different ways, one gene sequence can be used to make several different protein variants, depending on which exons are included. Normally splicing takes place in the nucleus of a cell, the cell’s control center where the DNA is stored. However, previous work from Dr. Eberwine’s lab has shown that splicing can also occur outside the nucleus, in a neuron’s cytoplasm. Dr. Eberwine’s latest paper demonstrates for the first time that one of the introns removed during cytoplamic splicing can regulate which form of BKCa channel protein is made, which in turn affects important electrical properties of the neuron. While introns used to be considered “junk DNA,” a number of studies, including Dr. Eberwine’s papers, are demonstrating that introns play crucial regulatory roles. Studying the process of splicing and intron removal in the production of BKCa channels may provide new insights about disorders of neuronal misfiring, such as epilepsy.
Bell TJ, Miyashiro KY, Sul JY, Buckley PT, Lee MT, McCullough R, Jochems J, Kim J, Cantor CR, Parsons TD, Eberwine JH. Intron retention facilitates splice variant diversity in calcium-activated big potassium channel populations. Proceedings of the National Academy of Sciences, 2010 Dec 7; 107(49): 21152-7. PMID: 21078998.
HANDBOOK FOR SMALL MOLECULE PROBES
The Molecular Libraries Program (MLP), a component of the NIH Common Fund, offers public sector biomedical researchers access to the large-scale screening capacity necessary to identify small molecules that can be optimized as chemical probes to study the functions of genes, cells, and biochemical pathways. This will lead to new ways to explore the functions of genes and signaling pathways in health and disease.
The Molecular Libraries Probe Production Centers Network (MLPCN), as part of the MLP, is a nationwide consortium of small molecule centers that produces innovative chemical tools for use in biological research. The MLPCN solicits novel assays from the research community for high throughput screening (HTS) against a library of 350,000 chemically diverse small molecules maintained in a central repository (the Molecular Libraries Small Molecule Repository; MLSMR). Validated screening hits are optimized by medicinal chemistry to produce useful in vitro chemical probes. All of the results from the MLPCN’s activities are deposited into an open access database, PubChem, for use in studying biology and disease.
The MLPCN brings together over 100 experienced medicinal chemists from five academic institutions and one NIH intramural center to focus on the development of high quality probes from screening hits. The lead medicinal chemists have extensive industrial experience from both biotech and large pharmaceutical companies. MLPCN probes cover highly diverse targets, biology and disease areas with many probes moving on as potential leads in drug discovery efforts after exiting the MLPCN.
This book brings together structure and biological information on the probes produced by the MLPCN in collaboration with the investigators who provided the screening assays. This information will be periodically updated with new probe information from the active MLPCN Centers.
NEW TOOLS TO CORRECT BRAIN ACTIVITY
Mouse neuron expressing Arch gene.Neuron expressing the Arch gene and generating light-activated proteins that are then localized to the outside of the neuron, where they can control the neuron’s activity in response to pulses of light. Credit: Courtesy of Brian Chow, Xue Han and Ed Boyden
Many neurological and psychiatric disorders are associated with abnormal activity in specific brain circuits. Historical approaches to correct abnormalities in brain circuits have relied on the use of electrical or magnetic stimulation, which only relieve the symptoms partially or for a short time. Although contemporary electromagnetic stimulation techniques have overcome many of the drawbacks of earlier approaches, a continuing and pressing need remains for new medical approaches to systematically correct abnormal brain function in patients with epilepsy, brain injury, and Parkinson’s disease.
A researcher in the Common Fund’s New Innovator program has engineered a powerful new class of tools to shut down nerve activity for short periods of time using different colors of light. These techniques are based on genes recovered from bacteria and fungi that encode light-activated proteins normally used for energy production in these organisms. When nerve cells expressing these proteins are exposed to the appropriate wavelength of light, they are prevented from transmitting electrical signals. When used in combination with genetic techniques to target these proteins to specific brain regions or cell subsets, these tools can lead to a much deeper understanding of the brain’s role in health and disease. The development of new technologies that allow precise control of neural circuits could lead to new treatments for disorders associated with abnormal brain activity, including chronic pain, epilepsy, brain injury, and Parkinson’s disease.
Chow BY, Han X, Dobry AS, Zian X, Chuong AS, Li M, Henninger MA, Belfort BM, Lin Y, Monahan PE, Boyden ES. High-performance genetically targetable optical neural silencing by light-driven proton pumps. Nature 2010 Jan 7;463(7277):98-102.
UNLOCKING THE MYSTERIES OF PROTEIN STRUCTURE FOR BETTER DRUG DEVELOPMENT
Researcher Uncovers Shape of Protein Important for Neurological Disorders
Dopamine is an essential "neurotransmitter", conveying important signals from one cell in the brain to another. Disruption of these signals initiated by dopamine can lead to schizophrenia, Parkinson’s disease, or drug addiction. The D3R protein is one of five dopamine receptor subtypes that bind dopamine to mediate cellular communication and is a primary target for the development of drugs to treat these conditions. Frequently, however, drugs that affect D3R can also affect the other dopamine receptor proteins and causing unwanted side effects. The Joint Center for Integral Membrane Protein Technologies-Complexes (JCIMPT-Complexes) at the Scripps Research Institute headed by Dr. Raymond C. Stevens, funded in part by the Common Fund’s Structural Biology program, has determined the three-dimensional shape of D3R, described in the November 19th advance online issue of the journal Science. This shape reveals subtle differences between D3R and the closely related protein D2R, which may assist researchers in designing effective D3R-specific drugs with fewer side effects. The research finding is particularly significant because D3R is a type of "membrane protein," a protein that is embedded in the viscous lipid environment surrounding a cell, making it challenging to isolate the protein to determine its shape. This finding comes soon after Dr. Stevens’ discovery of the shape of CXCR4, a protein important for HIV infection and cancer. By using methods similar to those pioneered by JCIMPT-Complexes and other research labs within the Structural Biology program, scientists have the potential to determine the structure of Image courtesy of Dr. Raymond Stevens many more proteins implicated in human diseases and develop more targeted therapeutic drugs.
Chien EY, Liu W, Zhao Q, Katritch V, Han GW, Hanson MA, Shi L, Newman AH, Javitch JA, Cherezov V, Stevens RC. Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science 2010 Nov 19; 330(6007): 1091-5. PMID: 21097933.
Researcher Determines Shape of a Protein Important for HIV and Cancer
The Joint Center for Integral Membrane Protein Technologies-Complexes (JCIMPT-Complexes) at the Scripps Research Institute headed by Dr. Raymond C. Stevens, funded in part by the Common Fund’s Structural Biology Program, has determined the three-dimensional structure of CXCR4, a cellular protein important for HIV infection as well as the growth and metastasis of many types of cancer. A recent paper by Dr. Stevens and colleagues, published in the October 7th advance online issue of the journal Science, describes the molecular structure of the CXCR4 protein bound to molecules known to inhibit CXCR4’s function. This study reveals that the location and the shape of the sites where inhibitory molecules bind is very different between CXCR4 and other closely related proteins. Using knowledge of these binding sites, researchers may one day develop new strategies to design drugs that bind CXCR4 to block HIV infection or stall the spread of some cancers.
Wu B, Chien EY, Mol CD, Fenalti G, Liu W, Katritch V, Abagyan R, Brooun A, Wells P, Bi FC, Hamel DJ, Kuhn P, Handel TM, Cherezov V, Stevens RC. Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 2010 Nov 19; 330(6007): 1066-71. PMID: 20929726.
November 30, 2010
SWEET DISCOVERY FOR PLANTS...AND HUMANS
Similar to humans, plants can be sickened by infection with bacteria and other pathogens, resulting in crop losses of over $500 billion every year. Dr. Wolf Frommer of the Carnegie Institution, funded in part by the Common Fund’s Metabolomics program, has identified how pathogens “hijack” plant cells to divert nutrients away from the plant for their own use. In the November 24th online edition of the journal Nature, Dr. Frommer and colleagues describe a new family of proteins, called SWEETs, which transport sugar out of the plant cell. Several different types of pathogens can cause increased production of SWEET proteins, thereby releasing more sugar from the plant cell to be consumed by the pathogen as food. Mutations in a rice SWEET protein confer resistance to bacterial blight, indicating that interfering with the action of SWEETs may provide a new method to block a broad range of pathogenic infections and reduce crop losses. Interestingly, SWEETs are present in animals as well, including mice and humans, and may play a role in sugar transport from liver and intestinal cells. A better understanding of SWEET proteins may have important implications for the health of plants and humans alike.
Chen LQ, Hou BH, Lalonde S, Takanaga H, Hartung ML, Qu XQ, Guo WJ, Kim JG, Underwood W, Chaudhuri B, Chermak D, Antony G, White FF, Somerville SC, Mudgett MB, Frommer WB. Sugar transporters for intracellular exchange and nutrition of pathogens. Nature, 2010 Nov 25; 468(7323): 527-32. PMID: 21107422.
NEW COMPOUND PREVENTS WEIGHT GAIN IN MICE
Dr. Jef Boeke at Johns Hopkins University, funded in part by the Common Fund's Technology Centers for Networks and Pathways (TCNP) program, has designed a compound that reduces weight gain in mice fed a high fat diet. In a paper published in the November 18th advance online edition of the journal Science, Dr. Boeke and colleagues show that the compound, called GO-CoA-Tat, interferes with the action of ghrelin, a hormone released from the gut that promotes weight gain. In order to function, ghrelin must be activated by another protein called GOAT (ghrelin O-acyltransferase). However, GO-CoA-Tat binds to GOAT and prevents it from activating ghrelin. Mice injected with GO-CoA-Tat had less activated ghrelin and gained less weight on a high fat diet than mice that received a placebo. Treatment with GO-CoA-Tat also improved the insulin response of the mice to a dose of glucose, a test similar to that used in humans to diagnose diabetes. Interestingly, mice treated with GO-CoA-Tat ate the same amount as mice treated with placebo, suggesting that GO-CoA-Tat regulates metabolism and not appetite. This study suggests a potential new drug target for the treatment of disorders such as diabetes, metabolic syndrome, and obesity.
Barnett BP, Hwang Y, Taylor MS, Kirchner H, Pfluger PT, Bernard V, Lin YY, Bowers EM, Mukherjee C, Song WJ, Longo PA, Leahy DJ, Hussain MA, Tschop MH, Boeke JD, Cole PA. Glucose and weight control in mice with a designed ghrelin O-acyltransferase inhibitor. Science, 2010 Dec 17; 330(6011): 1689-92. Epub 2010 Nov 18. PMID: 21097901.
COMMON FUND AWARDS $38.4M IN ARRA FUNDS IN FISCAL YEAR 2010
In fiscal year 2010, the NIH Common Fund made nine new American Investment and Recovery Act (ARRA) awards totaling $38.4M. All nine awards are “Building Sustainable Community-linked Infrastructure to Enable Health Science Research” grants (RC4) and each proposes a highly innovative program of research that cuts across multiple thematic areas for the NIH. Read More...
NEURONS FILTER OUT IRRELEVANT INFORMATION
Scientists have discovered how a small subset of neurons in the zebrafish brain has a big impact on an important behavior—the ability to hunt down prey. In a study published in the October 29th issue of Science, Dr. Herwig Baier of UC San Francisco and Dr. Ehud Isacoff of UC Berkeley, investigators in the Common Fund’s Nanomedicine program, use a novel fluorescent reporter of nerve cell activity to uncover how zebrafish can spot a tiny, one-celled paramecium against a complex visual background. The optic tectum in zebrafish is a layered structure that receives signals from the eye in the superficial layer, and sends signals from the deeper layer out to motor areas of the brain that control movement. Drs. Baier and Isacoff and colleagues demonstrate that a group of neurons in the optic tectum called superficial inhibitory neurons (SINs) acts to "filter out" large background patterns, allowing the tectum to send specific messages to motor areas about small, moving objects like prey. Silencing or destroying SINs eliminates this filtering, and impairs the zebrafish’s ability to catch prey. The selective filtering of irrelevant background information is found throughout the brain of many animals, including humans, but relatively little is known about the individual nerve cells that underlie this process. This study offers important insight about how circuits of nerve cells can provide background filtering, and suggests similar mechanisms may be found in human brains.
Del Bene F, Wyart C, Robles E, Tran A, Looger L, Scott EK, Isacoff EY, Baier H. Filtering of visual information in the tectum by an identified neural circuit. Science, 2010 Oct 29; 330 (6004): 669-73. PMID: 21030657.
HIGH THROUGHPUT STRATEGY FOR TESTING NERVE REGENERATION
Finding new drugs to promote regeneration of damaged nerve cells holds great promise for diseases such as Alzheimer's disease, spinal cord injury, brain trauma, and more. Many potential treatments, while promising in cell cultures, fail to promote regeneration in living animals. In a paper published October 13th in the Early Edition of the Proceedings of the National Academy of Sciences, Dr. Mehmet Yanik, a researcher at the Massachusetts Institute of Technology and an NIH Director's New Innovator awardee, demonstrates a novel method to rapidly screen potential drugs for their ability to promote nerve regeneration in the nematode C. elegans. Using this method, Dr. Yanik and colleagues discovered that compounds which regulate protein kinase C (PKC), an enzyme important for many different cellular processes, can modulate nerve regeneration after injury in specific neurons. The ability of this method to efficiently screen large numbers of potential drugs in living animals may greatly accelerate the discovery of new treatments to promote nerve regeneration.
Samara C, Rohde CB, Gilleland CL, Norton S, Haggarty SJ, Yanik MF. Large-scale in vivo femtosecond laser neurosurgery screen reveals small-molecule enhancer of regeneration. Proceedings of the National Academy of Sciences, 2010 Oct 26; 107(43): 18342-7. Epub 2010 Oct 11. PMID: 20937901.
EARLY INDEPENDENCE AWARDS JUMP START RESEARCH INDEPENDENCE
The National Institutes of Health announces the establishment of the NIH Director´s Early Independence Award (EIA) Program, a $60 million, 5-year initiative to support junior investigators in independent academic positions immediately following completion of their graduate research degrees. The NIH expects to issue 10 awards through this program in fall 2011. The EIA Program is intended to support exceptional early career scientists who possess the intellect, scientific creativity, drive, and maturity to flourish independently without the need for traditional post-doctoral training. The EIA grantees will be able to begin highly innovative and bold research programs as early in their careers as possible, increasing productivity and spurring pioneering research. NIH Director, Dr. Francis Collins, speaks out about the new initiative in a commentary in Nature, Vol.467, 7 October 2010.
DUAL NIH HONORS: TWO RESEARCHERS RECEIVE PIONEER AND T-R01 AWARDS
Treating a Parkinson's disease- like syndrome in rats using electrical stimulation of the spinal cord.
Miguel A. Nicolelis, M.D., Ph.D., neurobiologist and professor of neurobiology, biomedical engineering, and psychology and neuroscience at Duke University, will use the T-R01 Award to study dorsal spinal column stimulation as a novel alternative treatment of Parkinson's disease that is minimally invasive, easy to perform, and inexpensive. For his research under the Pioneer Award he will develop the first shared brain-controlled virtual reality environment designed to investigate brain-actuating technologies for treating neurological disorders.
J. Keith Joung, M.D., Ph.D., pathologist at Massachusetts General Hospital and professor of pathology at Harvard Medical School, is a molecular biologist with interests in protein engineering and molecular recognition. His Pioneer Award research will allow him to pursue developing more efficient methods for the generation, alteration, and differentiation of pluripotent stem cells. These broadly applicable approaches should accelerate the use of human stem cells for modeling of biological systems and for regenerative molecular medicine. His research under the T-R01 Award with fellow team members Paola Arlotta, Ph.D. at Massachusetts General Hospital / Harvard Medical School and Feng Zhang, Ph.D. at Massachusetts Institute of Technology will identify and apply new technologies that use molecular regulators to regenerate specific components of the nervous system and treat neurodegenerative diseases.
MILLIONS IN COMMON FUND AWARDS IN FY 2010
NIH Common Fund supports new research projects that cut across scientific disciplines and challenges conventional thinking.
September 13, 2010
GUT MICROBES CHANGED BY REPEATED ANTIBIOTIC USE
Repeated use of the antibiotic ciprofloxacin (Cipro) leads to persistent changes in the beneficial microbes of the gut, according to a study by David Relman, a researcher at Stanford University and recipient of an NIH Director's Pioneer Award. While ciprofloxacin usually does not cause gastrointestinal side effects normally associated with disturbance of gut-dwelling bacteria, this research demonstrates the occurrence of more subtle changes in gut microbe composition, such as replacement of some bacterial species with closely related species or eradication of some sub-sets of bacteria, particularly when multiple courses of antibiotics are administered. These long-term, persistent changes in microbe composition raise concerns about the evolution of antibiotic-resistant bacteria as well as chronic changes in pathogen-host interactions in the gut, regulation of host immunity, energy balance, or metabolism.
Dethlefsen L, Relman DA. Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proceedings of the National Academy of Sciences, 2011 Mar 15; 108 Suppl 1: 4554-61. Epub 2010 Sep 16. PMID: 20847294.
July 20, 2010
GENDER OF ALCOHOLIC PARENTS AND THEIR CHILDREN AFFECT PREVALENCE OF PSYCHIATRIC ILLNESS
Both the gender of an alcoholic parent and the gender of their children can affect the likelihood of those children developing certain types of psychiatric illness, according to a study by Marc Potenza and colleagues at Yale University School of Medicine, part of the Yale Center for Clinical Investigation supported by the Common Fund's Clinical and Translational Science Awards (CTSAs). While having an alcoholic parent of either gender increases a child's overall risk of developing a psychiatric illness, the risk of certain illnesses was affected by the gender of parent and child. For example, the odds of developing mania were significantly higher when the alcoholic parent and the child were of the same gender i.e. sons of alcoholic fathers and daughters of alcoholic mothers. Other disorders showed an opposite gender effectâ€”daughters of alcoholic fathers had an increased risk of abusing alcohol compared to sons, while sons of alcoholic mothers had an increased risk of panic disorder compared to daughters. Understanding how gender may influence risk of psychiatric illness in families with parental alcoholism may have important implications for prevention and treatment of at-risk children.
Morgan PT, Desai RA, Potenza MN. Gender-related influences of parental alcoholism on the prevalence of psychiatric illnesses: analysis of the National Epidemiologic Survey on Alcohol and Related Conditions. Alcoholism: Clinical and Experimental Research, 2010 Oct; 34(10): 1759-67. Epub 2010 Jul 20. PMID: 20645936.
July 8, 2010
NEW FY11 COMMON FUND PROGRAMS
New research programs, supported through the NIH Common Fund, are being launched in Fiscal Year 2011 to address critical needs and opportunities in a number of cross-cutting areas:
Planning Activities in FY2011
TINY DEVICE HELPS VIEW PROTEIN STRUCTURE
Researchers in the Common Fund's Structural Biology Research program have engineered a tiny new device to optimize the conditions needed for proteins to form crystals so their function can be studied in cells. Knowing a protein's structure can provide clues about how it functions normally, how it behaves abnormally in a diseased cell, and how its function may be restored by drugs that target specific parts of the protein that control activity
X-ray crystallography is a powerful tool to make high resolution images of protein structure by identifying the position of individual atoms in three-dimensional (3-D) space and then converting them into a topological map of the protein. However, for X-ray crystallography to work, the protein molecules must be concentrated and stacked in an orderly fashion into a protein crystal. Otherwise, the protein molecules just flop around, making it impossible to accurately pinpoint the position of the individual atoms. This is challenging because proteins are very finicky about the conditions under which they will form well-ordered crystals and very large amounts of proteins are usually needed to form crystals for analysis of 3-D structure.
Dr. Rustem Ismagilov at the University of Chicago has developed a microfluidic device called a "SlipChip" that allows researchers to explore the ideal conditions that can support the crystallization of a protein using very small amounts. The SlipChip can simultaneously test 160 different conditions that may support protein crystal formation. The protein of interest is injected in to a central port on the SlipChip where it flows through microfluidic channels and enters 160 nanometer-scale sized wells grouped into 16 separate units containing 10 wells each (see figure). The protein in each unit is subsequently exposed to a different precipitant, that is, a chemical solution that may support crystallization. This occurs after each precipitant is injected into one of the 16 units where it flows into 10 wells that sit underneath the protein-containing wells and the two are brought in to contact by "slipping"; the protein wells closer to the precipitant wells. The physical distance between the protein and precipitant wells on the SlipChip gradually increases from the first well to the tenth well, varying the time the protein and precipitant interact with each other. Precise control of this timing is important for some proteins that will not form well-ordered crystals if the interaction time is too fast. The beauty of the SlipChip is that it increases the chances of finding the optimum conditions for proteins and precipitants to interact so protein crystals form.
Li L, Du W, and Ismagilov RF. Multiparameter screening on SlipChip used for nanoliter protein crystallization combining free interface diffusion and microbatch methods. J Am Chem Soc. 2010 Jan 13;132(1):112-9. PMID: 20000709.
OVERCOMING OBSTACLES IN RESEARCH CULTURE: Q&A WITH DR. XAVIER CAGIGAS
Health research traditionally has been organized much like a series of cottage industries, lumping researchers into broad areas of scientific interest. Biomedical and behavioral research is complex and requires the expertise of teams of researchers from multiple scientific disciplines to speed its advance.
The broad goal for the NIH Common Find's Interdisciplinary Research Program is to change academic research culture to facilitate interdisciplinary approaches that dissolve academic department boundaries within academic institutions, increase cooperation between institutions, train scientists to cultivate interdisciplinary efforts, and build bridges between the biological sciences and the behavioral and social sciences.
The experience of Xavier E. Cagigas, Ph.D., Postdoctoral Research Fellow in Neurobehavioral Genetics and Neuropsychology at the UCLA Consortium for Neuropsychiatric Phenomics, exemplifies how this new interdisciplinary model of research can change academic research culture so that interdisciplinary approaches and team science are a normal mode of conducting research and scientists who pursue these approaches are adequately recognized and rewarded.
Common Fund Asks: Why is the interdisciplinary research model important?
Dr. Cagigas Responds: The greatest asset of interdisciplinary research is that it provides the academic freedom to pursue research questions which are situated at the confluence of various converging disciplines. The next generation of researchers poised to make a lasting impact on science and concomitantly decrease human suffering and bolster public health will come from these types of interdisciplinary settings.
What was the impact of interdisciplinary training on your career?
The NIH Common Fund's support of the UCLA Consortium for Neuropsychiatric Phenomics (CNP) created a unique interdisciplinary training environment that accelerated my career development, and brought me a step closer toward achieving my goal of establishing an independent research program. I have been very fortunate in receiving mentorship from both Drs. Robert Bilder and Nelson Freimer as a postdoctoral research fellow in neurobehavioral genetics and neuropsychology at UCLA. But beyond this, the interdisciplinary environment which has emerged in the CNP provided fertile ground for my own ideas and allowed me to contribute to and benefit from scientific discourse in a way that I never would have imagined at this stage of my career development.
How has interdisciplinary research facilitated your training and development?
Along my career trajectory, I have experienced both a more "traditional"; training environment as a graduate student and a truly interdisciplinary research community as an intern and postdoctoral fellow. I have learned that when a group of researchers reconfigure their research agendas in light of what their colleagues are also investigating, science moves forward at a much more rapid pace with a more coherent direction at various different levels of inquiry simultaneously.
Training in an interdisciplinary setting has allowed me to articulate my own voice and be heard earlier in my career than some of my colleagues who followed more traditional paths. Although it may be easier to begin to publish in a more discipline-specific training environment, I believe it is also more difficult to establish one's independence as a researcher. Postdoctoral training in an interdisciplinary environment helps trainees to find their own research niche more rapidly and opens the door to collaborations and other possibilities which are simply not possible in discipline-specific training settings laying the foundation for publication with a broader more integrated impact.
How will your experience with the interdisciplinary research model affect your future research endeavors?
This program opened my eyes to a new way of carrying out research that will have a significant impact on how my own program of scientific research develops and unfolds. I am committed to extending this interdisciplinary framework and am currently in the process of transitioning into a faculty role as we launch the UCLA Cultural Neuropsychology Initiative (CNI), a program to provide critically needed clinical services, training, and research relevant to the brain health of currently under-served and under-studied populations. This initiative is unique in its specific focus on the science of neuropsychology and will include: a clinical service to provide bilingual/bicultural neurocognitive and psychological assessments to the community, an integrated training program to help develop the next generation of culturally competent clinical and research neuropsychologists, and a new base for clinical and translational research with an explicit interdisciplinary and multicultural focus. Interdisciplinary research settings, such as the CNP and CNI, will undoubtedly continue to benefit the next generation of NIH-supported young investigators in new and exciting ways.
INNOVATIVE APPROACHES TO STUDY COMPLEX SIGNALING PATHWAYS IN CELLS
Researchers at John Hopkins University, led by Dr. Toru Komatsu and supported through the Common Fund’s Molecular Libraries and Imaging program, have developed a novel system to target and perturb specific molecular activities and communications pathways within cells. The technique may help elucidate the structure and function of complex signaling networks that perform basic functions within cells and may someday be targeted in disease therapies. The work was published in the journal Nature Methods (2010, 7(3):206-208).
GETTING PERSONAL WITH BACTERIA
Microbes, including bacteria, inhabit your body in great numbers and impact many aspects of health and disease such as obesity and Crohn's disease. Characterizing the genetic diversity of microbes that live in specific areas of the body is key to understanding the composition and dynamics of microbial communities within individuals, in transmission between individuals, and in transmission between individuals and the environment. The ability to characterize microbial diversity and transmission has been hampered in the past by a lack of high-throughput analysis tools. New computational tools being developed through the Common Fund's Human Microbiome Project (HMP) are accelerating microbiology and biomedical research, and unexpectedly, other fields like forensics.
Dr. Rob Knight, an investigator in the HMP, is developing novel approaches to analyze human microbial communities, and recently contributed to a paper in the Proceedings of the National Academy of Science on the discovery of "microbial fingerprints"; in a person's skin. The skin surface harbors a large number of bacteria that are highly diverse and yet personally unique from individual to individual. The bacteria are easily dislodged from the skin and transferred to objects upon contacting. By analyzing the "microbial fingerprint"; of bacteria left on computer equipment, Dr. Knight and colleagues at the University of Colorado found that the fingerprint could be traced to a specific individual with a high degree of certainty even if the objects had not been touched for two weeks. The approach could be important in forensic investigations to provide independent confirmation of forensic results obtained using more traditional methods such as human DNA analysis or fingerprinting.
Gaining Ground on Autism
The prevalence of autism in the United States has increased significantly over the past twenty years. While reasons for this increase remain elusive, the rise in autism rates continues to generate debate among scientist, caregivers and the public. Dr. Peter Bearman at Columbia University, a researcher in the Common Fund's Pioneer Award program, moves us one step closer to understanding why autism is increasing in California and identifying how local environmental and social factors may play a key role.
Using information from state birth records and case records of patients affiliated with the California Department of Health Services, Dr. Bearman and colleagues estimate that approximately 25 percent of the increased prevalence of autism observed in California between 1992 and 2005 is due to changes in how autism is diagnosed. The data also indicate that advanced maternal age poses a larger risk for autism than advanced paternal age. Because the effect of parental age on the rate of autism varies from year to year, the researchers speculate that variations in environmental or other factors may be associated with the extent of risk that can be attributed to parental age (King and Bearman, 2009; King et al., 2009).
Dr. Bearman and colleagues recently published that there are certain geographical areas of California where babies are more likely to develop autism. The finding of localized "clusters"; of autism suggests that environmental toxins or social factors such as increased public awareness and local advocacy may play a role. Using a spatial structure mapping technique, the researchers identified the high-risk clusters of autism based on residence at birth in California for children born from 1993 to 2001. Children born in a primary cluster have a four times greater risk for autism than children living in other parts of the state. While the study does not attempt to identify specific causes for autism, it does suggest that autism triggers could be environmental
King M and Bearman P. Diagnostic change and the increased prevalence of autism. Int J Epidemiol. 2009 Oct;38(5):1224-1234. PMID: 19737791.
- King MD, Fountain C, Dakhlallah, D and Bearman, P. Estimated autism risk and older reproductive age. Amer J Pub Health 2009 Sept;99(9):1673-1679. PMID: 19608957.
Clustering of Autism in California 1993-2001
This spatial clustering map shows a small area in California, North of Los Angeles, where there is a cluster of children born with autism. The children born in this part of the state are at four times greater risk for autism than children living in other parts of California. The risk is still present after adjusting for sex, birth order (firstborn or not), prenatal insurance status, preterm birth status, poor presentation at birth, low birth weight status, parental age, education, and race. The cluster consists of three separate regions centered around Santa Monica, Alhambra and North Hollywood. The area centered around North Hollywood is by far the largest. It has an approximate radius of 6 miles and is bounded by the South Central Regional Center to the South, the North Los Angeles regional center to the North, and Interstate 5 to the West.
NIH Announces New Common Fund Programs
New research programs and funding opportunities, supported through the NIH Common Fund, are being launched in Fiscal Year 2010 to address critical needs and opportunities in a number of cross-cutting areas:
- Science of Behavior Change
- Library of Integrated Network-Based Cellular Signatures (LINCS)
- Protein Capture Reagents
- Global Health
- Translational Applications of Stem Cells
- Knockout Mouse Phenotyping
- Regulatory Science
In addition, planning activities for Fiscal Year 2011 are underway in key areas: