The Effect of Lisinopril on the Desiccation Resistance of Drosophila melanogaster

Anagha Rama Varma

9/22/16

Background and Significance

Lisinopril is a drug approved by the FDA for use in treating high blood pressure in
humans. It works by restricting the Angiotensin Converting Enzyme (ACE) in the human reninangiotensin system (RAS). ACE converts the hormone angiotensin type 1 (Ang I) to angiotensin
type 2 (Ang II). Ang II is a vasoconstrictor; restricting ACE lowers the production of Ang II, and
thus lowers blood pressure. In addition to treatment of high blood pressure, the drug Lisinopril is
associated with many positive side effects, such as improved speed and reduced frailty. Many
studies have credited these effects to the drugs interaction with the human RAS. However, it has
been shown that Lisinopril-treated Drosophila melanogaster experience effects similar to those
observed in humans despite lacking RAS. D. melanogaster does contain a genetic pathway
similar to the one associated with RAS in humans. Therefore, it is possible that lisinoprils
effects may have a genetic link which is not yet fully understood.
Research Abstract
Analysis of gene expression has shown that Lisinopril effects changes in the expression
of certain genes in the midgut of Drosophila that are responsible for maintaining water-solute
balance in the organism. To better understand the effect of Lisinopril on this gene expression,
this study will examine the desiccation resistance of Lisinopril-treated Drosophila melanogaster
and compare it with that of untreated (control) flies. By identifying the effect, if such an effect
exists, of Lisinopril on desiccation resistance, the way in which Lisinopril affects gene
expression can be better understood. Specific genes and their interaction with the drug can then
be studied in order to better understand the workings of the drug. As the genetic pathway
connected to RAS in humans is conserved in Drosophila, understanding the effects of Lisinopril

on its expression in Drosophila can help to gain a better understanding of how the drug works in
humans and may help to reveal an overlooked genetic effect in humans.
Hypothesis
Lisinopril has been shown to have many positive side effects, such as improved strength
and longevity, which can be observed in lisinopril-treated Drosophila melanogaster. If lisinopriltreated Drosophila melanogaster are tested on desiccation resistance, they will perform better
than those that have not been treated.
Experimental Design
1) Expand lines 229, 304, and 73. 229 should be expanded to about 60 vials, whereas
2)
3)
4)
5)

304 and 73 should be expanded to about 80 vials each.

Clear adults after one week and mate emerging flies.
Clear adults after one week.
Collect virgin males. There should be at least eighty flies collected per line.
Maintain collected flies in six cages, two cages per line, with forty flies per cage (if

eighty were collected per line) using regular fly food.

6) One week before caged flies are five weeks old, collect new batch of virgin males.
Keep in separate set of three cages.
7) Begin feeding half of each set of flies (four weeks old and newly collected) drugged
food, while maintaining the rest on regular food.
8) Prepare vials for experiment: if eighty flies were collected per line, prepare sixty
vials. Thirty of the vials should be empty save for a cotton ball at the bottom; the
remaining vials should contain 4 grams anhydrous Drierite at the bottom, covered by
a cotton ball. The vials should be sealed using Parafilm.
9) Once the flies are five weeks and one week old, transfer to vials, four flies per vial.
Place the vials in ice and, once cold, begin collecting four flies at a time from a cage

via aspirator, and deposit in the vial. Quickly reseal the Parafilm. Label vials with line
number and treatment.
10) Observe and record, at hourly intervals, the number dead in each vial.