Mutagenesis as an Approach to Locate the Target of Anti-Parasitic Drug Compound KG3
Advisor Information
Paul Davis
Location
UNO Criss Library, Room 225
Presentation Type
Oral Presentation
Start Date
7-3-2014 10:00 AM
End Date
7-3-2014 10:15 AM
Abstract
Toxoplasma gondii is an obligate intracellular protozoan parasite that currently infects approximately one third of the global population. Toxoplasma gondii infections are a leading cause of birth defects and blindness. The parasite has also been found to cause complications in immunocompromised individuals and is suspected to play a role in the alteration of human behavior. Upon parasite exposure, two stages of infection occur. The first stage is known as the acute stage and is generally asymptomatic. Following the acute infection, the untreatable latent stage occurs. This stage results in a permanent, life-long infection that is non-life threatening in normal, healthy individuals but can be highly problematic for the immune compromised. In a previous experiment, novel drug compound KG3 was shown to be effective against the acute stage of toxoplasmosis. Chemical mutagenesis was performed using the mutagen N-ethyl-N-nitrosourea (ENU) and novel drug compound KG3 to identify the genetic target of the drug within the parasite. The application of ENU induced 10-100 base pair changes within the genome of each parasite. The mutagenized parasites were then grown in the presence KG3, and resistant parasites were produced. These parasites will be genetically sequenced for the purpose of locating the sequence within their genome that confers drug resistance. The genome of the drug resistant parasites will be compared to the genome of wild-type Toxoplasma gondii to locate the genotypic differences between the two strains. Variance between the strains would highlight the sequence responsible for conferring drug resistance to KG3.
Mutagenesis as an Approach to Locate the Target of Anti-Parasitic Drug Compound KG3
UNO Criss Library, Room 225
Toxoplasma gondii is an obligate intracellular protozoan parasite that currently infects approximately one third of the global population. Toxoplasma gondii infections are a leading cause of birth defects and blindness. The parasite has also been found to cause complications in immunocompromised individuals and is suspected to play a role in the alteration of human behavior. Upon parasite exposure, two stages of infection occur. The first stage is known as the acute stage and is generally asymptomatic. Following the acute infection, the untreatable latent stage occurs. This stage results in a permanent, life-long infection that is non-life threatening in normal, healthy individuals but can be highly problematic for the immune compromised. In a previous experiment, novel drug compound KG3 was shown to be effective against the acute stage of toxoplasmosis. Chemical mutagenesis was performed using the mutagen N-ethyl-N-nitrosourea (ENU) and novel drug compound KG3 to identify the genetic target of the drug within the parasite. The application of ENU induced 10-100 base pair changes within the genome of each parasite. The mutagenized parasites were then grown in the presence KG3, and resistant parasites were produced. These parasites will be genetically sequenced for the purpose of locating the sequence within their genome that confers drug resistance. The genome of the drug resistant parasites will be compared to the genome of wild-type Toxoplasma gondii to locate the genotypic differences between the two strains. Variance between the strains would highlight the sequence responsible for conferring drug resistance to KG3.