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Investigation of the Role of abl‐1 in the Apoptosis Pathways in C. elegans
Author(s) -
Vos Margaret R.,
Bennett Randy L.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.664.16
Subject(s) - apoptosis , mutant , microbiology and biotechnology , loss function , biology , function (biology) , wild type , mutation , phenotype , cancer research , genetics , gene
Apoptosis and engulfment of apoptotic cells is necessary for normal tissue development and remodeling. Although apoptosis is a natural phenomenon, it can be induced or halted by a variety of stressors. Induction of apoptosis is a possible way to treat cancerous cells in which desirable apoptosis has been halted. In our study, apoptosis was triggered in the model organism, Caenorhabditis elegans , using carcinogens to induce DNA damage in germline cells and then the different rates of apoptosis in various mutants were measured. This assay was performed on single‐mutant strains, to establish base levels of apoptosis for each strain, and then these single‐mutants were crossed with an abl‐1 mutant strain in order to analyze the impact of these loss‐of‐function mutation interactions. We showed that a loss of function in abl‐1 , when combined with another loss‐of‐function mutation directly involved in the targeted apoptosis pathway, aided in anti‐apoptotic promotion. CRISPR technology was used to increase the expression of abl‐1 in single mutants and wildtypes to see if a statistically significant impact on apoptosis occurred, and to serve as a comparison to the loss‐of‐function research. We found that increasing abl‐1 expression in wildtype worms acted in an anti‐apoptotic way, but in mutants where the traditional apoptosis pathway was impaired (e.g. those with loss‐of‐function mutations such as ced‐3 ), abl‐1 had a pro‐apoptotic function and could partially revive the pathway and promote apoptosis. This research is currently expanding to include a protocol focusing on analysis of somatic cell death, investigating the impact abl‐1 may have on EGL‐1. Our results demonstrate that C. elegans can serve as an in vivo model to study the mechanisms of mammalian DNA damage‐induced apoptosis. The concentration and time‐dependent responses in several mutant types and the manipulation of gene expression may provide information needed to develop more effective apoptosis‐based drug therapies. Support or Funding Information Funding was provided by the Biology Department at Juniata College. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). Assistance in developing CRISPR vector provided by Jason Chan, Ph.D., Juniata College. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .