Characterising the role of TEX12 in centrosome and cilia development

细胞分裂是生物体生长、发育和繁殖的基本过程。在哺乳动物中，有两种不同类型的细胞分裂，有丝分裂和减数分裂。有丝分裂允许我们通过产生与母细胞相同的两个子细胞来再生体细胞。相反，减数分裂对有性生殖至关重要，其特征是染色体数目减少，产生四个遗传多样性的单倍体子细胞。为了实现这种减数分裂，细胞分裂涉及一系列同步的染色体运动，最终在遗传重组中达到高潮，从而确保了物种的多样性。减数分裂的复杂本质是由一个特殊的突触复杂结构传递的，通常认为它除了促进减数分裂中的基因组重排外没有其他生物学功能。因此，突触复合蛋白被认为在健康体细胞中沉默以防止有丝分裂期间的基因组不稳定。然而，当研究失去一个叫做TEX12的突触复合体基因的影响时，我们意外地观察到大脑发育异常和肥胖。这些表型可能与一组称为纤毛病的疾病有关，其特征是纤毛的结构和功能缺陷。纤毛是在一些细胞表面发现的小的毛发状结构，它们在细胞过程中起着关键作用，比如感知和传递信号。该项目将采用活细胞成像和基因编辑来确定TEX12在纤毛形成中的作用。此外，我们将确定TEX12表达的调节因子，以了解何时在减数分裂之外正常产生TEX12。这种跨学科的方法将使我们能够确定TEX12是否是患者纤毛病的原因之一。

Cell division is a fundamental process critical for the growth, development, and reproduction of living organisms. In mammals, there are two distinct types of cell division, mitosis and meiosis. Mitosis allows us to regenerate somatic cells by generating two daughter cells identical to the mother cell. In contrast, meiosis is essential for sexual reproduction and is characterised by the reduction of chromosome number resulting in four genetically diverse haploid daughter cells. To achieve this meiotic cell division involves a series of synchronised chromosome movements culminating in genetic recombination which ensures the diversity of the species. The intricate nature of meiosis is delivered by a specialised synaptonemal complex structure generally assumed to have no biological function other than facilitating genomic rearrangements in meiosis. Consequently, synaptonemal complex proteins are believed to be silenced in healthy somatic cells to prevent genomic instability during mitosis. However, when investigating the effects of losing a synaptonemal complex gene called TEX12 we unexpectedly observed abnormal brain development and obesity. These phenotypes can be associated with a set of disorders called ciliopathies characterised by defects in the structure and function of cilia. Cilia are small hair-like structures found on the surface of some cells where they play a key role in cellular processes such as sensing and passing on signals. This project will employ live cell imaging and gene editing to determine the role TEX12 plays in cilia formation. Furthermore, we will identify regulators of TEX12 expression to understand when it is normally produced outside of meiosis. This cross-disciplinary approach will allow us to characterise if TEX12 is one of the causes of ciliopathy in patients.