Cel Male and female mammals differ in their sex chromosome complement: males have one X chromosome and one Y chromosome (XY), while females have two X chromosomes (XX). Decades of research have demonstrated that the Y chromosome is crucial for male fertility, regulating both sex differentiation and spermatogenesis. However, the role of the X chromosome in these critical stages of germ line development remains poorly understood.In this proposal, we will explore the functions of the X chromosome in the mammalian germ line. In eutherian mammals, sex determination is dependent on the Y-gene Sry, but in the other major mammalian class, the metatherians, it is controlled not only by a Y-locus, but also by the complement of X chromosomes. In Aim 1 we will apply CRISPR-mediated genome editing to metatherian mammals in order to identify these critical X and Y sex-determining genes. Our findings will provide insight into mammalian sex chromosome evolution and the aetiology of human sex differentiation disorders. In addition to its role in sex determination, the X chromosome is also predicted to become evolutionarily specialised for spermatogenesis. Consistent with this theory, we discovered that the mouse X chromosome is enriched in genes expressed exclusively in developing sperm. These genes are present in multiple copies, and together comprise an unprecedented 18% of the mouse X chromosome gene content. Many could be important candidates for unexplained male infertility. However, the functions of these genes have not been determined, because they cannot be manipulated using conventional gene targeting strategies. In Aim 2, we will use CRISPR to establish the roles of X-multicopy genes in male reproduction. Dziedzina nauki medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesmedical biotechnologycells technologiesstem cellsnatural sciencesbiological scienceszoologymammalogynatural sciencesbiological sciencesgeneticschromosomesnatural sciencesbiological sciencesgeneticsgenomes Słowa kluczowe Sex chromosomes germ cell development infertility Program(-y) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Temat(-y) ERC-CoG-2014 - ERC Consolidator Grant Zaproszenie do składania wniosków ERC-2014-CoG Zobacz inne projekty w ramach tego zaproszenia System finansowania ERC-COG - Consolidator Grant Instytucja przyjmująca THE FRANCIS CRICK INSTITUTE LIMITED Wkład UE netto € 1 912 369,00 Adres 1 MIDLAND ROAD NW1 1AT London Zjednoczone Królestwo Zobacz na mapie Region London Inner London — West Camden and City of London Rodzaj działalności Research Organisations Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 1 912 369,00 Beneficjenci (1) Sortuj alfabetycznie Sortuj według wkładu UE netto Rozwiń wszystko Zwiń wszystko THE FRANCIS CRICK INSTITUTE LIMITED Zjednoczone Królestwo Wkład UE netto € 1 912 369,00 Adres 1 MIDLAND ROAD NW1 1AT London Zobacz na mapie Region London Inner London — West Camden and City of London Rodzaj działalności Research Organisations Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 1 912 369,00