Illuminating the role of selfish genetic elements in somatic tissue homeostasis and aging

Introduction

Life-long tissue homeostasis requires sustained function of differentiated cell types as well as progenitor cells, which ensure tissue self-renewal. Little is known about the role that non-genic repetitive DNA sequences play in the maintenance of cellular homeostasis in diverse somatic tissues in vivo.

Transposable Elements

Transposable elements (TEs) are omnipresent, highly repetitive DNA sequences that mobilize and propagate within host genomes. Though previously thought to be fully repressed in the soma, TEs can be actively transcribed and, at least to some extent, mobile in certain somatic tissues.

Impact on Development and Disease

Indeed, somatic TE activity was proposed to contribute to normal development, aging, and pathologic conditions, such as cancer or neurodegeneration, underscoring the potential bearing that these selfish genetic elements could have in the soma. Nevertheless, the dynamics of activity and tissue-specific regulation of TE sequences are poorly understood, as is the impact of TE activity on different somatic cell types and tissues.

Recent Findings

We have recently uncovered that prevalent, tissue-specific TE mobility occurs in the Drosophila intestine and can lead to gene inactivation and tumor formation.

Research Objectives

Here, using this powerful and genetically amenable in vivo model system, I aim to combine genomic techniques with developmental and cell biology approaches to address the intriguing interplay between TEs and somatic tissue function in vivo. I will ask:

1. How does TE activity differ between diverse cell types and how does it change in a tissue under normal or pathological conditions, as well as during aging?
2. What processes control TE activity in somatic cells in vivo?
3. What are the direct consequences of TE transcriptional activity and mobility on somatic cell function, and the long-term impacts at a tissue and organism level?

Conclusion

Ultimately, the proposed research program will shed new light on the importance of mobile DNA sequences in the maintenance of lifelong tissue homeostasis in vivo.