Developmental mechanisms controlled by Myt 1 kinase

我的实验室研究果蝇发育过程中细胞如何繁殖和分化。这些发育机制的缺陷与不孕不育、衰老和癌症有关。我们的研究重点是一种古老的细胞周期调节机制，它从酵母到人类都是保守的。我们正在研究一种名为dMyt1的蛋白质的作用，这种蛋白质抑制细胞周期进程的某些方面，这些方面由另一种名为CDK1的蛋白质控制，CDK1是细胞分裂的主要调节因子。Myt1似乎起到了CDK1“刹车”的作用，在细胞试图分裂之前，确保许多协调步骤的重要生物过程正确完成。我们还对释放Myt1刹车机制的方法感兴趣，这样细胞就可以在准备好的时候分裂。通过对果蝇myt1突变体的研究，我们已经证明Myt1活性的丧失会导致男性不育，并与某些组织中额外的、缺陷的细胞有关。我们已经在myt1突变的精子前体细胞中发现了特定的亚细胞缺陷，这可能是导致男性不育的原因。为了从功能上表征dMyt1的这一作用，我们培育了转基因菌株，用于在精子发生期间表达不同形式的蛋白质。通过比较正常和myt1突变体寻找Myt1功能的线索，这些工具将使我们能够设计实验来测试所提出的模型，以了解Myt1亚细胞定位和催化活性是如何调节的。这些实验将阐明Myt1活性如何影响雄性减数分裂，并有望揭示有助于我们理解Myt1在其他发育阶段的功能的特征。

My laboratory studies how cells reproduce and differentiate during Drosophila development. Defects in these developmental mechanisms are associated with infertility, aging and cancer. Our research focuses on an ancient cell cycle regulatory mechanism, which has been conserved from yeast to humans. We are characterizing the role of a protein called dMyt1 that inhibits certain aspects of cell cycle progression that are controlled by another protein called Cdk1, which functions as a master regulator of cell division. Myt1 seems to function like a Cdk1 "brake", ensuring that important biological processes with many coordinated steps are properly completed, before cells attempt to divide. We are also interested in ways of releasing this Myt1 brake mechanism, so that cells can divide when they are ready. By studying Drosophila myt1 mutants, we have shown that loss of Myt1 activity causes male sterility and is associated with extra, defective cells in certain tissues. We have identified specific sub-cellular defects in myt1 mutant sperm precursor cells that probably account for the male sterility. To functionally characterize this role of dMyt1, we have generated trangenic strains for expressing different forms of the protein during spermatogenesis. By comparing normal and myt1 mutants for clues to Myt1 function, these tools will enable us to design experiments to test proposed models for understanding how Myt1 sub-cellular localization and catalytic activity are regulated. These experiments will clarify how Myt1 activity influences male meiosis and are also expected to reveal features that will help us to understand Myt1 functions at other stages of development.