DISSERTATION RESEARCH: Developmental breakdown and abnormal growth in hybrid dwarf hamsters

生物学的一个主要目标是了解生物多样性的起源。新物种的来源和持久性与物种之间成功繁殖的障碍的形成密切相关。在哺乳动物中出现的一个常见障碍是杂交胎盘的异常发育，导致杂交后代异常大或小。这种反复出现的模式表明，在哺乳动物杂交中，控制发育的基因和分子途径可能经常被破坏。我们将使用杂交矮仓鼠的几个实验来弥合我们对极端胚胎和胎盘过度生长的遗传原因的理解的重大差距。首先，大胎盘和正常大小胎盘的高通量DNA测序实验将用于确定导致过度生长的基因组区域。其次，基因组实验将用于确定胎盘中基因调控的破坏是否会导致杂交过度生长。总之，这些实验将使用一个强大的实验室模型，开始揭示哺乳动物在发育早期异常生长的遗传原因。这项工作将使用尖端的方法来解决哺乳动物物种形成和分化的本质的基本问题。这项研究还将通过深入了解胎盘和胚胎发育异常的遗传原因，推进对发育性疾病的研究。此外，拟议的活动将为研究生提供培训和支持，并促进对本科生的指导。

A major goal in biology is to understand the origin of biological diversity. The source and persistence of new species is closely linked to the formation of barriers to successful reproduction between species. One common barrier that arises in mammals is abnormal development of hybrid placentas resulting in unusually large or small hybrid offspring. This recurrent pattern indicates that the genes and molecular pathways that control development may often be disrupted in mammalian hybrids. We will use several experiments with hybrid dwarf hamsters to bridge significant gaps in our understanding of the genetic causes of extreme embryonic and placental overgrowth. First, high-throughput DNA sequencing experiments of large- and normal-sized placenta will be used to identify areas of the genome that cause overgrowth. Second, genomic experiments will be used to determine if the disruption of gene regulation in the placenta causes hybrid overgrowth. Together, these experiments will use a powerful laboratory model to begin to uncover the genetic causes of abnormal mammalian growth during the early stages of development. This work will use cutting-edge methods to address fundamental questions on the nature of species formation and divergence in mammals. This research will also advance the study of developmental diseases by providing insights into the genetic causes of abnormal growth in developing placentas and embryos. Furthermore, the proposed activities will provide training and support for a graduate student and facilitate the mentoring of undergraduate students.