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[
Chembiochem,
2003]
I never expected to spend most of my life studying worms. However, when the time came for me to choose an area for my postdoctoral research, I was intrigued both with the problems of neurobiology and with the approaches of genetics. Having heard that a new "genetic organism" with a remarkably simple nervous system was being explored by Sydney Brenner - the microscopic soil nematode Caenorhabditis elegans - I decided to join Sydney in his efforts.
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[
Chembiochem,
2003]
The title of my lecture is "Nature's gift to Science". It is not a lecture about one scientific journal paying respect to another, but about how the great diversity of the living world can both inspire and serve innovation in biological research. Current ideas of the uses of model organisms spring from the exemplars of the past and choosing the right organism for one's research is as important as finding the right problems to work on. In all of my research these two decisions have been closely intertwined. Without doubt, the fourth winner of the Nobel prize this year is Caenorhabditis elegans; it deserves all of the honour but, of course, it will not be able to share
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[
Biogerontology,
2002]
This is a personal account of the early days in the genetic analysis of aging when it was difficult to persuade the world that there were genes that specified life prolongation. I describe the situation in 1980 and briefly describe the background of early work on the nematode Caenorhabditis elegans and my role in the revolution in aging research that has occurred in the last 20 years.
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[
Ann N Y Acad Sci,
1959]
As consulting editor, I saw and now take the opportunity to amalgamate concepts scattered in the papers that follow. My hope also is to bring a certain unity to the heterogeneous studies contributed by the imaginative and resourceful workers who created the program of the conference on which this monograph is based. Axenic cultivation, the rearing of one or more individuals of a single species on a nonliving medium, dominates microbiology. Axenic cultures, usually referred to as "pure cultures", are fundamental to identification of many protists (bacteria, algae, fungi, and protozoa) and to their exploitation in research...
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Exp Gerontol,
2006]
Caenorhabditis elegans has been used to model aspects of a number of age-associated neurodegenerative diseases, including Alzheimer''s, Parkinson''s and Huntington''s diseases. These models have typically involved the transgenic expression of disease-associated human proteins. Here I describe my laboratory''s specific experience engineering C. elegans models of Alzheimer''s disease, and give a general consideration of the advantages and disadvantages of these C. elegans models. The type of insights that might be gained from using these (relatively) simple models are highlighted. In particular, I consider the potential these models have for uncovering common and unique fundamental toxic mechanisms underlying human neurodegenerative diseases.
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Exp Gerontol,
2013]
This communication will briefly review more than 30 years of research on aging using the nematode Caenorhabditis elegans ("The Worm") as carried out in the labs of Tom Johnson. We will highlight research directions initiated in the 1980's, which were exciting for those of us trying to turn over a new leaf in aging research. In this narrative, I will discuss primarily the science that I and my lab have been involved with for the last 30 years. This area has been fascinating to those studying the sociology of science as modern aging research has moved to replace the simplistic, poorly controlled and outright fictitious approaches seen in much of the previous aging research.
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Am J Physiol Cell Physiol,
2005]
Systems biology is an emerging discipline focused on tackling the enormous intellectual and technical challenges associated with translating genome sequence into a comprehensive understanding of how organisms are built and run. Physiology and systems biology share the goal of understanding the integrated function of complex, multicomponent biological systems ranging from interacting proteins that carry out specific tasks to whole organisms. Despite this common ground, physiology as an academic discipline runs the real risk of fading into the background and being superseded organizationally and administratively by systems biology. My goal in this article is to discuss briefly the cornerstones of modern systems biology, specifically functional genomics, nonmammalian model organisms and computational biology, and to emphasize the need to embrace them as essential components of 21st-century physiology departments and research and
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[
Prog Brain Res,
1995]
Research over the last twenty years on the nematode Caenorhabditis elegans has provided a wealth of information on the structure and development of the nervous system of this animal. For example, complete descriptions of the cellular anatomy (including synaptic contacts) and of the lineage derivation of each of the 302 neurons of the adult C. elegans hermaphrodite are known. Moreover, numerous classical and molecular techniques are available to characterize genes that direct the development and function of cells within the nervous system. Research in my laboratory has used these techniques to study a set of six touch receptor neurons. In this chapter I will describe some of the lessons we have learned about how these cells acquire their specific characteristics (and other cells do not) and how the cells function as touch receptors.
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[
Harvey Lect,
1988]
Animal development involves a complex pattern of cell divisions ultimately leading to the generation of a highly diverse complement of cell types. What are the molecular mechanisms responsible for controlling patterns of cell division and for causing cells to become different from one another? To address the problem, my colleagues and I have been examining how genes control cell lineage and cell fate in the nematode Caenorhabditis elegans. The study of C. elegans was pioneered by Sydney Brenner (1973, 1974), who selected this organism because it is highly tractable genetically (e.g., see Herman, 1988)and because it is simple and essentially invariant in its cellular anatomy (the adult hermaphrodite is now known to contain a total of 959 somatic cell nuclei; Sulston and Horvitz, 1977; Kimble and Hirsh, 1979; Sulston et al., 1983). The invariance in C. elegans anatomy reflects a similar invariance in development. For example, the cell lineage of C. elegans is essentially the same in all individuals (Sulston and Horvitz, 1977; Kimble and Hirsh, 1979; Sulston et al., 1983). This cell lineage was determined by direct observation of living nematodes: individual nuclei were watched with the aid of Nomarski optics as they migrated,
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[
Life Sci,
2006]
Alzheimer''s disease (AD) is affecting larger and larger proportions of our population as lifespan increases. Thus, the means to prevent or reduce the rate of this disorder is a high priority for medical research. A standardized extract of Ginkgo biloba leaves EGb 761 is a popular dietary supplement taken by the general public to enhance mental focus and by the elderly to delay onset of age-related loss of cognitive function. EGb 761 has been used for treatment of certain cerebral dysfunctions and dementias associated with aging and AD. Substantial evidence indicates that EGb 761 has neuroprotective effects. But, mechanisms of action of the components of the extract are, unfortunately, poorly understood. Research in my laboratory focuses on understanding mechanisms of action of the components of the herbal extract EGb 761 in protection against Alzheimer''s disease. We have demonstrated that EGb 761 inhibited amyloid beta aggregation in vitro and attenuates reactive oxidative species (ROS) in a model organism - the round worm Caenorhabditis elegans. Furthermore, EGb 761 eased its toxicity in the transgenic C. elegans. We also found that only a certain size of the amyloid beta aggregates is toxic to the worms. These findings suggest that EGb 761 has a clear therapeutic potential for prevention and/or treatment of AD. A better understanding of the mechanisms of neuroprotection by EGb 761 will be important for designing therapeutic strategies, for basic understanding of the underlying neurodegenerative processes, and for a better understanding of the effectiveness and complexity of this herbal medicine.