1 PhD project offered in the IPP winter call 2023/2024
Diploid organisms contain a maternal and a paternal genome complement. A characteristic feature of a diploid karyotype is that the chromosomes and genes are present in correct proportion with respect to each other, which is referred to as gene dosage. Having two sets of chromosomes provides robustness and allows developmental progression when genetic perturbations occur in heterozygosity. However, a subset of genes are highly dosage sensitive: either an increase or decrease in copy number can reduce fitness and ultimately lead to organismal death.
Sex chromosomes are an interesting exception, as female humans contain two X chromosomes, while males have only one X and one Y chromosome. To account for these differences in copy number, the production of X-linked genes is corrected by dosage compensation. This epigenetic mechanism orchestrated by chromatin-modifying activities and noncoding RNAs ensures a collective finetuning of hundreds of genes on the X chromosome.
Sex differences are highly relevant in mosquitos, as only female mosquitoes feed on blood and are thereby able to transmit infectious diseases. Understanding sex differences and sex chromosomes has major implications for opening up new ways to control e.g. malaria by controlling its vector. However, our current knowledge of the molecular mechanisms regulating sex chromosomes and dosage compensation is utterly limited to only three model organisms (fruit flies, nematodes, and mice). Excitingly, our group has recently discovered the first component of the X chromosome dosage compensation pathway in the malaria mosquito Anopheles gambiae (Kalita et al., in revision).
PhD project: Characterization of a novel dosage compensation mechanism
The PhD student will work on the molecular mechanisms underlying this entirely new form of gene dosage control. We will use next-generation sequencing and mass spectrometry to characterize the downstream effectors responsible for this compensatory mechanism. We will then explore the cellular and genomic regulation of these pathways using molecular biology, screening and microscopy approaches.
We are looking for a PhD student with a strong interest in mechanisms of gene regulation, genomics, evolutionary biology and/or biochemistry. Our ideal candidate would like to combine wet lab and computational approaches. If you are a team player and have a high level of motivation and enthusiasm for science, you are the right person for our group.
If you are interested in this project, please select Keller Valsecchi as your group preference in the IPP application platform.
Publications relevant to this project
Basilicata MF and Keller Valsecchi CI (2021) The good, the bad, and the ugly: Evolutionary and pathological aspects of gene dosage alterations. PLOS Genet, 17:e1009906 Link
Keller Valsecchi CI*# , Marois E*, Basilicata MF*, Georgiev P and Akhtar A# (2021) Distinct mechanisms mediate X chromosome dosage compensation in Anopheles and Drosophila. Life Sci Alliance, 4:e202000996 (*indicates joint contribution, # indicates joint correspondence) Link
Keller Valsecchi CI*, Basilicata MF*, Georgiev P, Gaub A, Seyfferth J, Kulkarni T, Panhale A, Semplicio G, Manjunath V, Holz H, Dasmeh P and Akhtar A (2021) RNA nucleation by MSL2 induces selective X chromosome compartmentalization. Nature (*indicates joint contribution) Link
Adrian-Kalchhauser I, Sultan SE, Shama LNS, Spence-Jones H, Tiso S, Keller Valsecchi CI and Weissing FJ (2020) Understanding “non-genetic” inheritance: insights from molecular-evolutionary crosstalk. Trends Ecol Evol Link
Furman BLS, Metzger DCH, Darolti I, Wright AE, Sandkam BA, Almeida P, Shu JJ, Mank JE (2020) Sex Chromosome Evolution: So Many Exceptions to the Rules. Genome Biol Evol. Jun 1;12(6):750-763. Link
Kalita AI, Marois E, Basilicata MF, Kozielska M, Weissing FJ, Jaouen E, Möckel M, Rühle F, Butter F, Keller Valsecchi CI. The sex-specific factor SOA establishes X chromosome dosage compensation in Anopheles mosquitos (in revision).