How do cells control gene dosage alterations during evolution and disease?

Our team explores the epigenetic mechanisms and physiological relevance of gene dosage in regulating cellular function in male and female animals - from individual genes to chromosome-wide scales.

A protein complex (green) plays a pivotal role in gene dosage compensation in male fruit flies.

Sexually reproducing animals contain two genome copies - one from each parent. Deviations from this twofold dosage can lead to diseases such as cancer. Paradoxically, dosage changes are key to evolution and occur naturally in sex chromosomes; men have one X chromosme, but women have two. We study the gene-regulatory mechanisms upon dosage alterations, their impact on developmental and evolutionary processes and ask how they shape male and female physiology.

Dosage and sex-bias in development and disease
In humans, females shut down one copy of the X chromosome through epigenetic silencing. However, some genes escape this repressive state providing females an advantage that males do not possess. We study the tissue-specific mechanisms of escape and their relevance for sex-bias in human diseases.  

Evolutionary epigenetics of sex chromosomes
Only female mosquitoes feed on blood and transmit malaria, yet sex differences remain understudied in non-model organisms. In malaria mosquitoes, we recently identified SOA, a male-specific factor that upregulates X-linked genes. In some species, such as crustaceans, environmental factors like temperature can influence sex. We investigate how environment impacts gene regulation and chromatin dynamics.

Towards a better understanding of female-male differences
A deep understanding of sex chromosome regulation and dosage compensation across species will provide fundamental insights into epigenetic mechanisms and their evolution. They may also identify new targets for controlling malaria transmission, help understand how animal development may be impacted by climate change and provide new insights in sex-biased diseases in humans.

The research group led by Claudia Keller Valsecchi will be starting at the Biozentrum in August 2025.