- Email: [email protected]
The Buck Institute for Age Research
S. Melov / Experimental Gerontology 36 (2001) 205±208
Experimental Gerontology 36 (2001) 205±208
205
www.elsevier.nl/locate/expgero
Pro®le of Gerontological Institutions
The Buck Institute for Age Research S. Melov*, V. Dodge Buck Institute for Age Research, 8001 Redwood Blvd., Novato, CA 94945, USA Received 14 September 2000; received in revised form 14 December 2000; accepted 14 December 2000
The Buck Institute is an independent, non-pro®t research institute, based in Novato, CA, approximately 30 miles north of San Francisco. Dedicated entirely to research on aging and age-associated diseases, it is the only institute of its kind in the United States, and only one of three in the world. The faculty, comprising researchers with diverse backgrounds in a variety of disciplines, are provided with an environment and state-ofthe-art tools to maximize intellectual creativity and productivity, without other demands on their time. Born in controversy, the Institute began as a desire of philanthropist Beryl Buck, to ªextend help toward the problems of the aged.º When she died in 1977, she left a substantial portion of her estate to Marin County, CA, where she had been a resident for 40 years. After many years of legal wrangling between various factions over the substantial funds from the Buck Trust, the courts designated funding for the Buck Institute as one of three major projects located in Marin for the bene®t of ªall humankind.º A board of scienti®c advisors decided that the focus of the Buck Institute should be basic research into the mechanisms of aging and age-associated diseases such as Alzheimer's disease, Parkinson's disease (PD), stroke, and cancer. Following further protest from community activists opposed to new development in Marin County, the Buck Institute ®nally opened its doors in July 1999. By July 2000, the ®rst phase of recruitment was complete, bringing the complement of faculty to 12, and the total number of researchers to 66. Designed by world-renowned architect I.M. Pei, the campus is not only aesthetic and functional, but promotes an atmosphere of interaction and collaboration among researchers (Fig. 1). The Buck Institute is also home to three centralized, state-of-the-art core facilities that provide Buck Institute faculty, as well as outside researchers with the resources, infrastructure, and expertise necessary to conduct experiments involving genomics, imaging, and mass spectrometry.
* Tel.: 11-415-899-1800; fax: 11-415-209-2232. E-mail address: [email protected] (S. Melov). 0531-5565/01/$ - see front matter q 2001 Elsevier Science Inc. All rights reserved. PII: S 0531-556 5(01)00085-7
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S. Melov / Experimental Gerontology 36 (2001) 205±208
Fig. 1. The Buck Institute for Age Research. Five different views are shown of the Buck Institute, including the spectacular atrium just outside of the main auditorium, and the projected ®nal appearance of the institute with all ®ve buildings complete.
1. Brief overview of current faculty interests Founding President and CEO Dr Dale Bredesen has endeavored to recruit leading researchers in neurodegenerative diseases, models of aging, genomics, and other specialties. Bredesen is studying the basic chemistry and critical mechanisms of neural cell death in the major age-associated neurodegenerative diseases Ð including Alzheimer's disease and PD in cell culture models (Lu et al. 2000). Dr David Greenberg studies both cell culture and animal models relating to molecular mechanisms of nerve cell injury in stroke and related cerebrovascular disorders (Jin et al. 2000). He is also Vice President of Special Research Programs, which
S. Melov / Experimental Gerontology 36 (2001) 205±208
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include postdoctoral courses on a wide range of issues related to aging and agerelated disease, and a variety of topical seminars on the latest advances in aging research. Considered one of the foremost authorities in the world on mitochondrial physiology, Dr David Nicholls is studying mitochondrial mechanisms with a view to understanding why nerve cells die as a result of stroke and other age-related diseases such as PD and Alzheimer's disease (Nicholls and Ward 2000). By utilizing methodologies that include cell culture systems, culture-free systems, and transgenic model organisms, Dr Lisa Ellerby focuses on molecular mechanisms of cell death (Ellerby and Bredesen 2001). Using models of mitochondrial oxidative stress, including Caenorhabditis elegans and superoxide dismutase 2 (mitochondrial SOD) mutant mice, Dr Simon Melov is working to understand what role reactive oxygen species generated by the mitochondria play in the aging process itself (Melov et al., 2000). The main focus of Dr Michael Ellerby's research is on developing new therapies for cancer. In 1999, Dr Ellerby led a team of investigators to invent ªHunter-Killerº peptides (HKPs), an innovative and promising cancer therapy (Ellerby et al., 1999). The major goal of Dr Julie Andersen's research is to understand the molecular events that lead to PD. Andersen (Andersen, 2000) carries out these studies with transgenic mouse models as well as cell culture models of PD. An expert on breast cancer research and treatment, Dr Christopher Benz is Director of the Program on Cancer and Developmental Therapeutics. The Benz lab is working to de®ne critical receptor systems involved in human breast tumor development. Dr Vivian Hook's main areas of interest involve proteases Ð particularly their involvement in age-associated neurodegenerative diseases such as Alzheimer's disease (Hook and Mende-Mueller, 2000). The ultimate goal of this research is the development of therapeutic strategies involving the creation of compounds that will inhibit these proteases. Joining the faculty of the Buck Institute in the summer of 2001, Dr Gordon Lithgow's area of expertise is in the genetics of aging and stress, utilizing the nematode Caenorhabditis elegans. Dr Bradley Gibson brings the bene®t of his extensive expertise in protein and carbohydrate mass spectrometry, as well as peptide and protein chemistry, to his role as Director of the Chemistry Core. Working with the Co-Director of the Chemistry Core, Dr Vivian Hook, Gibson will provide the other faculty members of the Buck Institute with the resources and support to conduct experiments involving mass spectrometry and proteomic analysis. An expert in genomics, gene expression and bioinformatics, Dr Mark Eshoo is the Director of the Genomics Core, a facility open to both Buck Institute researchers and outside researchers. Services available include Laser Capture Microdissection (LCM) Ð which allows researchers to isolate and examine individual cells from tissue samples, and DNA microarray technology. Buck Institute researchers have used microarrays for studies on cell differentiation (distinguishing, for example, between cells that are young and old, healthy and diseased), time course experiments (which can study the progression of gene expression over time), and the detection of genetic mutations. Dr Eshoo is also developing a network-accessible, multi-platform, user-friendly database of microarray data of gene expression of aging.
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S. Melov / Experimental Gerontology 36 (2001) 205±208
As Director of the Morphology Core, Dr Paul Goldsmith provides Buck Institute and outside researchers with the ability to analyze cell culture and tissue samples using the most advanced bright®eld, ¯uorescence, laser confocal, and transmission electron microscopy. Other services include immunostaining and in situ hybridization analysis of genetic samples, image capture and recording using state-of-the-art CCD technology and highresolution digital video, and computerized image analysis. He is also striving to make the Buck Institute an innovative leader in the ®eld of applied imaging technology. 2. Summary With its state-of-the-art facilities, research-centered approach, and diverse faculty, the Buck Institute is in a unique position to further aging research. While the ®rst stage of the Buck Institute's development is complete, plans for future development include the construction of three more laboratory buildings, increasing the campus from 185,000 to 355,000 square feet; addition of several more investigators with expertise in model systems of aging; development of more advanced models of aging; and further recruitment of experts in the mechanisms of age-associated diseases. There can be no doubt that there is an urgent need for knowledge about the aging process and diseases associated with senescence. By the year 2030 in the United States alone, the number of people 65 and older will double to 70 million, the number of Alzheimer's cases will increase from 4 million to 9 million, and the ensuing health care costs will increase to over $2 trillion. Recognition of this impending demographic shift continues to increase in the general public, the media, and the government. Positive actions have resulted Ð such as President Clinton's allocation of $50 million of government funds over the next 5 years for Alzheimer's research. Given this heightened awareness of the dif®culties associated with advanced age, corresponding moves to action, and increased funding, the future of aging research looks to be an exciting one. References Andersen, J.K., 2000. Ubiquitin accumulation in Parkinson's disease. Mech. Ageing Dev. (in press). Ellerby, L.M., Bredesen, D.E., 2001. Measurement of cellular redox and antioxidant enzymes during apoptosis. Methods Enzymol. in press. Ellerby, M.H., et al., 1999. Anti-cancer activity of targeted pro-apoptotic peptides. Nat. Med 5, 1032±1038. Hook, V.Y.H., Mende-Mueller, L., 2000. Proteolytic mechanisms in neurodegenerative diseases. In: Chesselet, M.F. (Ed.). Molecular mechanisms of neurodegenerative diseases. Humana Press, Totowa, NJ (in press). Jin, K.L., Mao, X.O., Greenberg, D.A., 2000. Vascular endothelial growth factor: direct neuroprotective effect in in vitro ischemia. Proc. Natl. Acad. Sci. USA in press. Lu, D.C., Rabizadeh, S., Chandra, S., Shayya, R.F., Tenney, K.A., Ellerby, L.M., Krajewski, S., Ye, X., Salvesen, G.S., Koo, E.H., Bredesen, D.E., 2000. A second cytotoxic proteolytic peptide derived from a-amyloid precursor protein. Nat. Med. 6, 397±404. Melov, S., et al., 2000. Extension of life-span with superoxide dismutase/catalase mimetics. Science 289, 1567±1569. Nicholls, D.G., Ward, M.W., 2000. Mitochondrial membrane potential and cell death: mortality and millivolts. Trends Neurosci. 23, 166±174.
Experimental Gerontology 36 (2001) 205±208
205
www.elsevier.nl/locate/expgero
Pro®le of Gerontological Institutions
The Buck Institute for Age Research S. Melov*, V. Dodge Buck Institute for Age Research, 8001 Redwood Blvd., Novato, CA 94945, USA Received 14 September 2000; received in revised form 14 December 2000; accepted 14 December 2000
The Buck Institute is an independent, non-pro®t research institute, based in Novato, CA, approximately 30 miles north of San Francisco. Dedicated entirely to research on aging and age-associated diseases, it is the only institute of its kind in the United States, and only one of three in the world. The faculty, comprising researchers with diverse backgrounds in a variety of disciplines, are provided with an environment and state-ofthe-art tools to maximize intellectual creativity and productivity, without other demands on their time. Born in controversy, the Institute began as a desire of philanthropist Beryl Buck, to ªextend help toward the problems of the aged.º When she died in 1977, she left a substantial portion of her estate to Marin County, CA, where she had been a resident for 40 years. After many years of legal wrangling between various factions over the substantial funds from the Buck Trust, the courts designated funding for the Buck Institute as one of three major projects located in Marin for the bene®t of ªall humankind.º A board of scienti®c advisors decided that the focus of the Buck Institute should be basic research into the mechanisms of aging and age-associated diseases such as Alzheimer's disease, Parkinson's disease (PD), stroke, and cancer. Following further protest from community activists opposed to new development in Marin County, the Buck Institute ®nally opened its doors in July 1999. By July 2000, the ®rst phase of recruitment was complete, bringing the complement of faculty to 12, and the total number of researchers to 66. Designed by world-renowned architect I.M. Pei, the campus is not only aesthetic and functional, but promotes an atmosphere of interaction and collaboration among researchers (Fig. 1). The Buck Institute is also home to three centralized, state-of-the-art core facilities that provide Buck Institute faculty, as well as outside researchers with the resources, infrastructure, and expertise necessary to conduct experiments involving genomics, imaging, and mass spectrometry.
* Tel.: 11-415-899-1800; fax: 11-415-209-2232. E-mail address: [email protected] (S. Melov). 0531-5565/01/$ - see front matter q 2001 Elsevier Science Inc. All rights reserved. PII: S 0531-556 5(01)00085-7
206
S. Melov / Experimental Gerontology 36 (2001) 205±208
Fig. 1. The Buck Institute for Age Research. Five different views are shown of the Buck Institute, including the spectacular atrium just outside of the main auditorium, and the projected ®nal appearance of the institute with all ®ve buildings complete.
1. Brief overview of current faculty interests Founding President and CEO Dr Dale Bredesen has endeavored to recruit leading researchers in neurodegenerative diseases, models of aging, genomics, and other specialties. Bredesen is studying the basic chemistry and critical mechanisms of neural cell death in the major age-associated neurodegenerative diseases Ð including Alzheimer's disease and PD in cell culture models (Lu et al. 2000). Dr David Greenberg studies both cell culture and animal models relating to molecular mechanisms of nerve cell injury in stroke and related cerebrovascular disorders (Jin et al. 2000). He is also Vice President of Special Research Programs, which
S. Melov / Experimental Gerontology 36 (2001) 205±208
207
include postdoctoral courses on a wide range of issues related to aging and agerelated disease, and a variety of topical seminars on the latest advances in aging research. Considered one of the foremost authorities in the world on mitochondrial physiology, Dr David Nicholls is studying mitochondrial mechanisms with a view to understanding why nerve cells die as a result of stroke and other age-related diseases such as PD and Alzheimer's disease (Nicholls and Ward 2000). By utilizing methodologies that include cell culture systems, culture-free systems, and transgenic model organisms, Dr Lisa Ellerby focuses on molecular mechanisms of cell death (Ellerby and Bredesen 2001). Using models of mitochondrial oxidative stress, including Caenorhabditis elegans and superoxide dismutase 2 (mitochondrial SOD) mutant mice, Dr Simon Melov is working to understand what role reactive oxygen species generated by the mitochondria play in the aging process itself (Melov et al., 2000). The main focus of Dr Michael Ellerby's research is on developing new therapies for cancer. In 1999, Dr Ellerby led a team of investigators to invent ªHunter-Killerº peptides (HKPs), an innovative and promising cancer therapy (Ellerby et al., 1999). The major goal of Dr Julie Andersen's research is to understand the molecular events that lead to PD. Andersen (Andersen, 2000) carries out these studies with transgenic mouse models as well as cell culture models of PD. An expert on breast cancer research and treatment, Dr Christopher Benz is Director of the Program on Cancer and Developmental Therapeutics. The Benz lab is working to de®ne critical receptor systems involved in human breast tumor development. Dr Vivian Hook's main areas of interest involve proteases Ð particularly their involvement in age-associated neurodegenerative diseases such as Alzheimer's disease (Hook and Mende-Mueller, 2000). The ultimate goal of this research is the development of therapeutic strategies involving the creation of compounds that will inhibit these proteases. Joining the faculty of the Buck Institute in the summer of 2001, Dr Gordon Lithgow's area of expertise is in the genetics of aging and stress, utilizing the nematode Caenorhabditis elegans. Dr Bradley Gibson brings the bene®t of his extensive expertise in protein and carbohydrate mass spectrometry, as well as peptide and protein chemistry, to his role as Director of the Chemistry Core. Working with the Co-Director of the Chemistry Core, Dr Vivian Hook, Gibson will provide the other faculty members of the Buck Institute with the resources and support to conduct experiments involving mass spectrometry and proteomic analysis. An expert in genomics, gene expression and bioinformatics, Dr Mark Eshoo is the Director of the Genomics Core, a facility open to both Buck Institute researchers and outside researchers. Services available include Laser Capture Microdissection (LCM) Ð which allows researchers to isolate and examine individual cells from tissue samples, and DNA microarray technology. Buck Institute researchers have used microarrays for studies on cell differentiation (distinguishing, for example, between cells that are young and old, healthy and diseased), time course experiments (which can study the progression of gene expression over time), and the detection of genetic mutations. Dr Eshoo is also developing a network-accessible, multi-platform, user-friendly database of microarray data of gene expression of aging.
208
S. Melov / Experimental Gerontology 36 (2001) 205±208
As Director of the Morphology Core, Dr Paul Goldsmith provides Buck Institute and outside researchers with the ability to analyze cell culture and tissue samples using the most advanced bright®eld, ¯uorescence, laser confocal, and transmission electron microscopy. Other services include immunostaining and in situ hybridization analysis of genetic samples, image capture and recording using state-of-the-art CCD technology and highresolution digital video, and computerized image analysis. He is also striving to make the Buck Institute an innovative leader in the ®eld of applied imaging technology. 2. Summary With its state-of-the-art facilities, research-centered approach, and diverse faculty, the Buck Institute is in a unique position to further aging research. While the ®rst stage of the Buck Institute's development is complete, plans for future development include the construction of three more laboratory buildings, increasing the campus from 185,000 to 355,000 square feet; addition of several more investigators with expertise in model systems of aging; development of more advanced models of aging; and further recruitment of experts in the mechanisms of age-associated diseases. There can be no doubt that there is an urgent need for knowledge about the aging process and diseases associated with senescence. By the year 2030 in the United States alone, the number of people 65 and older will double to 70 million, the number of Alzheimer's cases will increase from 4 million to 9 million, and the ensuing health care costs will increase to over $2 trillion. Recognition of this impending demographic shift continues to increase in the general public, the media, and the government. Positive actions have resulted Ð such as President Clinton's allocation of $50 million of government funds over the next 5 years for Alzheimer's research. Given this heightened awareness of the dif®culties associated with advanced age, corresponding moves to action, and increased funding, the future of aging research looks to be an exciting one. References Andersen, J.K., 2000. Ubiquitin accumulation in Parkinson's disease. Mech. Ageing Dev. (in press). Ellerby, L.M., Bredesen, D.E., 2001. Measurement of cellular redox and antioxidant enzymes during apoptosis. Methods Enzymol. in press. Ellerby, M.H., et al., 1999. Anti-cancer activity of targeted pro-apoptotic peptides. Nat. Med 5, 1032±1038. Hook, V.Y.H., Mende-Mueller, L., 2000. Proteolytic mechanisms in neurodegenerative diseases. In: Chesselet, M.F. (Ed.). Molecular mechanisms of neurodegenerative diseases. Humana Press, Totowa, NJ (in press). Jin, K.L., Mao, X.O., Greenberg, D.A., 2000. Vascular endothelial growth factor: direct neuroprotective effect in in vitro ischemia. Proc. Natl. Acad. Sci. USA in press. Lu, D.C., Rabizadeh, S., Chandra, S., Shayya, R.F., Tenney, K.A., Ellerby, L.M., Krajewski, S., Ye, X., Salvesen, G.S., Koo, E.H., Bredesen, D.E., 2000. A second cytotoxic proteolytic peptide derived from a-amyloid precursor protein. Nat. Med. 6, 397±404. Melov, S., et al., 2000. Extension of life-span with superoxide dismutase/catalase mimetics. Science 289, 1567±1569. Nicholls, D.G., Ward, M.W., 2000. Mitochondrial membrane potential and cell death: mortality and millivolts. Trends Neurosci. 23, 166±174.