Biomedical subjects

R Branicky

Publications and source records attributed to R Branicky.

3 recordsLinked to original sources

PubMed2001

Why only time will tell.

The nematode Caenorhabditis elegans has become a model system for the study of the genetic basis of aging. In particular, many mutations that extend life span have been identified in this organism. When loss-of-function mutations in a gene lead to life span extension, it is a necessary conclusion that the gene normally limits life span in the wild type. The effect of a given mutation depends on a number of environmental and genetic conditions. For example, the combination of two mutations can result in additive, synergistic, subtractive, or epistatic effects on life span. Valuable insight into the processes that determine life span can be obtained from such genetic analyses, especially when interpreted with caution, and when molecular information about the interacting genes is available. Thus, genetic and molecular analyses have implicated several genes classes (daf, clk and eat) in life span determination and have indicated that aging is affected by alteration of several biological processes, namely dormancy, physiological rates, food intake, and reproduction.

Aging↗

PubMed2001

Phenotypic and suppressor analysis of defecation in clk-1 mutants reveals that reaction to changes in temperature is an active process in Caenorhabditis elegans.

Mutations in the Caenorhabditis elegans maternal-effect gene clk-1 affect cellular, developmental, and behavioral timing. They result in a slowing of the cell cycle, embryonic and postembryonic development, reproduction, and aging, as well as of the defecation, swimming, and pharyngeal pumping cycles. Here, we analyze the defecation behavior in clk-1 mutants, phenotypically and genetically. When wild-type worms are grown at 20 degrees and shifted to a new temperature, the defecation cycle length is significantly affected by that new temperature. In contrast, we find that when clk-1 mutants are shifted, the defecation cycle length is unaffected by that new temperature. We carried out a screen for mutations that suppress the slow defecation phenotype at 20 degrees and identified two distinct classes of genes, which we call dsc for defecation suppressor of clk-1. Mutations in one class also restore the ability to react normally to changes in temperature, while mutations in the other class do not. Together, these results suggest that clk-1 is necessary for readjusting the defecation cycle length in response to changes in temperature. On the other hand, in the absence of clk-1 activity, we observe temperature compensation, a mechanism that maintains a constant defecation period in the face of changes in temperature.

Animals↗

PubMed2000

clk-1, mitochondria, and physiological rates.

Mutations in the C. elegans maternal-effect gene clk-1 are highly pleiotropic, affecting the duration of diverse developmental and behavioral processes. They result in an average slowing of embryonic and post-embryonic development, adult rhythmic behaviors, reproduction, and aging.(1) CLK-1 is a highly conserved mitochondrial protein,(2,3) but even severe clk-1 mutations affect mitochondrial respiration only slightly.(3) Here, we review the evidence supporting the regulatory role of clk-1 in physiological timing. We also discuss possible models for the action of CLK-1, in particular, one proposing that CLK-1 is involved in the coordination of mitochondrial and nuclear function. BioEssays 22:48-56, 2000.

Amino Acid Sequence↗