Keller Valsecchi/Huylmans
Epigenetics and sex chromosomes through the lens of evolution
Supervisor: Claudia Keller Valsecchi
Co-Supervisor: Ann Kathrin Huylmans
Scientific Background
Many plants and animals contain a naturally tolerated monosomy, the heteromorphic sex chromosomes. In species, where the male is the heterogametic sex, males have only a single X and Y chromosome (e.g. humans or fruit flies). Conversely, there are other species (e.g. chicken or butterflies), where female oocytes contain either a Z or W chromosome, while males are homogametic, i.e. have identical chromosomal complements in their germ cells. To correct for dosage imbalance due to sex chromosomes, cells contain a gene regulatory mechanism termed Dosage Compensation (DC) (Ohno, 1966). Sex chromosomes evolve from autosomes, a process that occurs rapidly and is characterized by recurrent turnovers and decay. These ever-changing chromosomal landscape poses constant challenges for gene regulatory mechanisms such as DC, because the X/Z need to be distinguished from autosomes.
More recently, the presence or absence of DC could be studied in various non-model organism. This revealed a fascinating diversity, with some species exhibiting complete DC; others, which exhibit DC only in certain stages or tissues; some with incomplete DC, where only certain dosage-sensitive genes are balanced; and others, where DC is completely absent (Furman et al., 2020). The underlying mechanisms and reasons for these differences across taxa are entirely unknown. This diversity will be the core of a PhD project in our group at the interface between evolution, epigenetics and gene regulation.
Project description
The PhD project aims at exploring the diversity of DC mechanisms in an organism with ZW sex chromosomes: the brine shrimp Artemia franciscana (Huylmans et al., 2019). We have recently identified a histone modification associated with upregulation of the Z chromosome of Artemia females. You will characterize DC factors during brine shrimp development. Importantly, early embryonic development in this organism can manifest in two different pathways depending on whether environmental conditions are favorable (ovoviviparous) or not (oviparous). Hence you will systematically compare the sensitivity of those two pathways and environmental conditions to DC. In our studies, it will be an unprecedented advantage that the invertebrate Artemia can be easily grown and is amenable to experiments in the lab and hence, will be used for establishing genetic manipulations of putative DC candidates by RNAi or CRISPR/Cas9.
What you will learn
During this project, you will become proficient in techniques related to epigenomics (RNA-/ChIP-seq/Cut&Run), spatial and in-situ genomics, genome engineering, microscopy, FISH techniques and bioinformatics. You will learn how to independently develop your ideas, pursue a research project and communicate your results in oral and written form. This includes developing skills such as critical thinking, working and collaborating in an international environment, project management, writing and public speaking, for example by attending international conferences. Besides the training program and courses of the Genevo RTG, we will support you in your career planning.
Your qualifications
We are looking for a student with a strong interest in epigenetics, developmental biology and evolution. Our ideal candidate would like to combine wet lab, imaging/microscopy and computational approaches (pre-existing training is not necessary). In our team, scientists from various nationalities are working together on diverse aspects of gene dosage from evolution to disease. Hence, we would like to work with a candidate that is enthusiastic about moving this project forward in an international and multidisciplinary environment. If you are a team player and show a high degree of motivation and excitement for science, you will be the right person to join our group.
Publications relevant to this project
Ohno S (1966) Sex Chromosomes and Sex-linked Genes. Springer, Berlin, Heidelberg.
Furman BLS, Metzger DCH, Darolti I, Wright AE, Sandkam BA, Almeida P, et al. (2020) Sex Chromosome Evolution: So Many Exceptions to the Rules. Genome Biol Evol. 12: 750–763. doi.org/10.1093/gbe/evaa081
Kalita AI, Marois E, Kozielska M, Weissing FJ, Jaouen E, Möckel MM, Rühle F, Butter F, Basilicata MF and Keller Valsecchi CI (2023) The sex-specific factor SOA controls dosage compensation in Anopheles mosquitos. Nature , 623:175–182. doi.org/10.1038/s41586-023-06641-0
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 (2020) RNA nucleation by MSL2 induces selective X chromosome compartmentalization. Nature, 589:137-142 (*indicates joint contribution). doi.org/10.1038/s41586-020-2935-z
Huylmans AK, Toups MA, Macon A, Gammerdinger WJ, Vicoso B (2019) Sex-Biased Gene Expression and Dosage Compensation on the Artemia franciscana Z-Chromosome. Genome Biol Evol. 11: 1033–1044. doi.org/10.1093/gbe/evz053