Modulation of Endogenous TSC Signalling during Kidney Development

• Applicant: Dr. Daniel Romaker
• Subject Area: Developmental Biology
• Term: from 2010 to 2012
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 188396934

Control of organ size is a complex sequence of interdependent transduction pathways. Defective transmission in these hubs often results in diseases as cancer or polycystic kidney diseases (PKD). A central interface relaying signals is the tuberous sclerosis (TSC) complex composed of TSC1 and TSC2. Mutations in these genes are responsible for hamartomas, non-invasive benign tumors affecting many organs such as brain, lung, skin, heart and kidney. The TSC complex is a significant regulator of mammalian target of Rapamycin (mTOR) which is also one of the mayor modulators controlling cell growth and cell cycle progression. Aberrant mTOR signalling has been extensively studied as a cause/consequence for different cancers and PKD. Recently microRNAs (miRNAs), a family of small, non-coding RNAs, triggering mRNA degradation, have also been linked to governing proliferation and contribute to cancer progression. But so far no relevant data is available linking miRNA and TSC/mTOR signalling directly to organ growth control. Therefore, we address to investigate upstream components relaying signals in the TSC complex during kidney development and hence how these signals are controlled and integrated to prevent aberrant TSC signalling. We account for a better understanding of TSC signalling in the kidney as we want to investigate endogenous signal transduction and additionally include miRNAs as potent negative or fine tune regulators in kidney growth control. The conclusions drawn by this study will help to better understand aberrant TSC signalling leading to PKD and cancer.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Oliver Wessely