Wittbrodt LabOpen Positions

Investigation of gene-environment interactions in medaka and identification of genes that influence individual pollutant responses

Background

Human-made substances, such as pharmaceuticals and environmental toxins, are increasingly entering our ecosystems, raising significant concerns. Current risk assessment methods often overlook individual differences in how organisms are affected by these pollutants, treating these variations as mere statistical errors.

Acknowledging the pivotal role of genetic diversity in driving individual responses to pollutants, we are conducting a large-scale genome-wide association study (GWAS) in the teleost fish medaka (Oryzias latipes). We use drug-induced heart rate changes as a general indicator for a physiological response to explore how genetic polymorphisms and environmental factors (GxE) interact to influence individual susceptibility.

We make use of a unique resource consisting of a large number of genetically distinct Medaka Inbred lines, the MIKK Panel, to precisely control for genetic background and understand the mechanistics of individual pollutant responses from the molecular to the organismic level.

Phenotypic examination of 72 genetically distinct MIKK panel lines revealed clear, strain-dependent differences in heart rate response to ethanol, disulfiram and caffeine. In a subsequent F2 segregation analysis based on extreme line crosses, we identified several quantitative trait loci (QTL) that exhibit GxE interactions and are associated with individual responses to ethanol exposure. 

Functional validation studies of candidate genes with CRISPR/Cas9 and base editors are currently being carried out. 

Scope of the Bachelor’s Thesis

The aim of this project is to analyze the phenotypes of F2 crosses and characterize their response to caffeine/disulfiram. The candidate will be involved in preparing medaka embryos for Illumina sequencing, which includes DNA extraction and potentially library preparation. 

Depending on your motivation and availability, the scope of work can be adjusted according to your interests. 

If you are a highly motivated student who enjoys working independently and the project has awakened your interest, please get in touch with philip.watson@cos.uni-heidelberg.de and jochen.wittbrodt@cos.uni-heidelberg.de

 The start date is as soon as possible.

Investigation of gene-environment interactions in medaka and identification of genes that influence individual pollutant responses

Background

Human-made substances, such as pharmaceuticals and environmental toxins, are increasingly entering our ecosystems, raising significant concerns. Current risk assessment methods often neglect individual differences in how organisms are affected by these pollutants, treating these variations as mere statistical errors.

Acknowledging the pivotal role of genetic diversity in driving individual responses to pollutants, we are conducting a large-scale genome-wide association study (GWAS) in the teleost fish medaka (Oryzias latipes). We use drug-induced heart rate changes as a general indicator for a physiological response to explore how genetic polymorphisms and environmental factors (GxE) interact to influence individual susceptibility. Using the Medaka Inbred Kiyosu Karlsruhe (MIKK) panel allows us to precisely control for genetic background and environmental exposure, and understand the mechanistics of individual pollutant responses from the molecular to the organismic level.

Phenotypic examination of 72 genetically distinct MIKK panel lines revealed clear, strain-dependent differences in heart rate response to ethanol, disulfiram and caffeine. In a subsequent F2 segregation analysis based on extreme line crosses, we identified several quantitative trait loci (QTL) that exhibit GxE interactions and are associated with individual responses to ethanol exposure. 

Additional F2 segregation results on individual disulfiram/caffeine responses will be available soon. 

Scope of the Master’s Thesis

The main aim of this project is to perform functional validation studies on candidate genes found in all QTL mapping studies. The candidate will use CRISPR/Cas9 and base editing tools for this. Additionally, the following experiments are anticipated: in situ hybridization, enzyme activity assays, and measurements of embryonic metabolites. Depending on your motivation and availability, the scope of work can be adjusted according to your interests. 

If you are a highly motivated student who enjoys working independently and the project has awakened your interest, please get in touch with philip.watson@cos.uni-heidelberg.de and jochen.wittbrodt@cos.uni-heidelberg.de 

The anticipated start is August or September.