The Effect Of Stress On Drosophila Deficient In Werner Protein

Charlotte Salameh, Northeastern Illinois University

Description

Stress affects a wide-range of biochemical and physiological processes including metabolism, development, and aging. Environmental stressors such as chemical exposure, diet, and temperature can cause free radicals that can damage DNA and lead to mutations. Proteins such as Werner (WRN) help to maintain genomic stability due to their involvement in DNA repair and replication. In humans, mutations in WRN cause Werner syndrome (WS), an autosomal disease characterized by accelerated aging and predisposition to cancer. In Drosophila melanogaster (fruit flies), mutations in the Drosophila homolog of WRN, WRNexo, lead to similar phenotypes as Werner patients, such as shortened lifespan, high tumor incidence, and muscle degradation. Therefore we can use WRNexo mutant flies (WRNexo  ) to study the link between stress, aging, and disease. Because very little is known about the impact of thermal stress on genome stability, we tested the response of WRNexo  mutant flies (WRNexo  ) to varying thermal environments during larval and adult developmental stages. To assess larval sensitivity, WRNexo  heterozygous larvae were reared on cornmeal agar and stored in an 18°C, 25°C (control), or 29°C incubator. Thermal sensitivity was determined by the percent of WRNexo  homozygotes exposed to 18 °C and 29 °C that survive to adulthood compared to the percent control WRNexo  homozygotes. To assess adult sensitivity, activity of individual WRNexo  and wild type adult flies was monitored at regular intervals using a Drosophila Activity Monitor. We expected to observe a decrease in larval survival and reduced active periods in adult flies exposed to 18°C and 29°C due to the inability of the mutants to cope with thermal stress. We found that WRNexo  larvae were not sensitive to thermal stress as shown by their high relative survival percentages at 18°C and 29°C. Thermal stress affected adult locomotor activity in a sex-specific manner. While average locomotor activity did not differ between WRNexo  and wild type for either sex at 18°C and 25°C, a significant reduction in locomotor activity was observed in female WRNexo  mutants when exposed to 29°C. When we looked at diurnal activity patterns, we found that the evening activity peaks present in wild type flies were absent in WRNexo  flies, although these results were only significant in females at 29°C. These results would suggest that WRNexo  may have roles in protecting female adult flies against thermal stress induced by warmer temperatures. Our results contribute to a broader knowledge of the involvement of WRN in genome longevity and the molecular mechanisms involved in stress. Overall, this knowledge can be used to benefit the general public by developing new approaches to regulate aging and age-associated diseases.

 
Apr 19th, 12:00 AM

The Effect Of Stress On Drosophila Deficient In Werner Protein

Stress affects a wide-range of biochemical and physiological processes including metabolism, development, and aging. Environmental stressors such as chemical exposure, diet, and temperature can cause free radicals that can damage DNA and lead to mutations. Proteins such as Werner (WRN) help to maintain genomic stability due to their involvement in DNA repair and replication. In humans, mutations in WRN cause Werner syndrome (WS), an autosomal disease characterized by accelerated aging and predisposition to cancer. In Drosophila melanogaster (fruit flies), mutations in the Drosophila homolog of WRN, WRNexo, lead to similar phenotypes as Werner patients, such as shortened lifespan, high tumor incidence, and muscle degradation. Therefore we can use WRNexo mutant flies (WRNexo  ) to study the link between stress, aging, and disease. Because very little is known about the impact of thermal stress on genome stability, we tested the response of WRNexo  mutant flies (WRNexo  ) to varying thermal environments during larval and adult developmental stages. To assess larval sensitivity, WRNexo  heterozygous larvae were reared on cornmeal agar and stored in an 18°C, 25°C (control), or 29°C incubator. Thermal sensitivity was determined by the percent of WRNexo  homozygotes exposed to 18 °C and 29 °C that survive to adulthood compared to the percent control WRNexo  homozygotes. To assess adult sensitivity, activity of individual WRNexo  and wild type adult flies was monitored at regular intervals using a Drosophila Activity Monitor. We expected to observe a decrease in larval survival and reduced active periods in adult flies exposed to 18°C and 29°C due to the inability of the mutants to cope with thermal stress. We found that WRNexo  larvae were not sensitive to thermal stress as shown by their high relative survival percentages at 18°C and 29°C. Thermal stress affected adult locomotor activity in a sex-specific manner. While average locomotor activity did not differ between WRNexo  and wild type for either sex at 18°C and 25°C, a significant reduction in locomotor activity was observed in female WRNexo  mutants when exposed to 29°C. When we looked at diurnal activity patterns, we found that the evening activity peaks present in wild type flies were absent in WRNexo  flies, although these results were only significant in females at 29°C. These results would suggest that WRNexo  may have roles in protecting female adult flies against thermal stress induced by warmer temperatures. Our results contribute to a broader knowledge of the involvement of WRN in genome longevity and the molecular mechanisms involved in stress. Overall, this knowledge can be used to benefit the general public by developing new approaches to regulate aging and age-associated diseases.