1st year MSc (Interdisciplinary Biomedical Research). The student will be assigned to a PhD project prior to the 2nd year of study.

在胎盘哺乳动物中，怀孕涉及植入胚胎和子宫粘膜或子宫内膜之间的双向交流1固有的染色体不稳定性使得人类胚胎的遗传组成和发育潜力非常不同。2我们先前的研究表明，当为怀孕做好最佳准备时，子宫内膜作为胚胎适合性的生物传感器，能够同时支持高适合性胚胎的发育，并通过类似月经的机制消除低质量胚胎。1，2这种现象被称为‘着床检查点’。越来越多的证据表明，在受孕周期中未能建立一个强大的植入检查点，会创造一个既不选择低适合度胚胎也不支持高质量胚胎的子宫内膜植入环境；这两种情况都会导致流产。2、3该项目的目的是(I)对控制着床时胚胎-子宫内膜通讯的受体-配体相互作用进行细粒度的深入了解，(Ii)确定与生殖失败相关的病理子宫内膜状态如何影响着床时胚胎的生物传感和选择。该项目与MRC的分子和细胞医学主题相一致，旨在发现新的孕前诊断生物标志物和治疗靶点，以减轻与反复流产相关的高身体、心理和经济负担。该项目利用了Brosens实验室现有的独特资源，包括获取新鲜的子宫内膜组织和生物库样本(&gt；5000)；从导致植入失败、流产或活产的试管受精胚胎中获取用过的培养液；以及从植入窗口获得的35例子宫内膜活检组织的单细胞转录数据(包括空间转录切片)。此外，奥特教授还将在分析复杂的大型数据集方面提供专业知识。

Pregnancy in placental mammals involves bi-directional communication between the implanting embryo and the uterine mucosa or endometrium.1 Intrinsic chromosome instability renders human embryo extremely diverse in their genetic makeup and developmental potential.2 Our previous studies indicated that, when prepared optimally for pregnancy, the endometrium acts as a biosensor for embryo fitness, capable of simultaneously supporting the development of high-fitness embryos and eliminating low-quality embryos through a menstruation-like mechanism.1,2 This phenomenon has been termed the 'implantation checkpoint'. Growing evidence suggests that failure to establish a robust implantation checkpoint in a conception cycle creates an endometrial implantation environment that neither selects against low-fitness embryos nor supports high-quality embryos; both scenarios lead to miscarriage.2,3 The aims of the project are (i) to gain granular insights into the receptor-ligand interactions that control embryo-endometrial communication at implantation and (ii) to define how pathological endometrial states associated with reproductive failure impact on embryo biosensing and selection at implantation. This project, which aligns with the molecular and cellular medicine theme of the MRC, is designed to uncover novel pre-pregnancy diagnostic biomarkers and therapeutic target to mitigate the high physical, psychological, and economical burden associated with recurrent miscarriage. The project capitalises on the unique resources available in the Brosens' lab, including access to fresh endometrial tissues and bio-banked samples (>5000); access to spent culture medium from IVF embryos that resulted in implantation failure, miscarriage, or live birth; and single cell transcriptomic data (including spatial transcriptomics) on 35 endometrial biopsies obtained across the implantation window from patients with and without prior reproductive failure. In addition, Professor Ott will provide expertise in the analysis of complex large data sets.