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

胎盘哺乳动物的妊娠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人类胚胎在遗传组成和发育潜力方面极其多样化。2我们以前的研究表明，当为妊娠做好最佳准备时，子宫内膜充当胚胎适应性的生物传感器，能够同时支持高适应性胚胎的发育，并通过类似于受精的机制消除低质量胚胎。1，2这种现象被称为“植入检查点”。越来越多的证据表明，未能在受孕周期中建立一个强大的植入检查点，会创造一个子宫内膜植入环境，既不选择低适应性胚胎，也不支持高质量胚胎;两种情况都导致流产。2，3该项目的目的是（i）获得控制着床时胚胎-子宫内膜通讯的受体-配体相互作用的颗粒状见解，以及（ii）确定与生殖失败相关的病理性子宫内膜状态如何影响植入时的胚胎生物传感和选择。该项目符合MRC的分子和细胞医学主题，旨在发现新的孕前诊断生物标志物和治疗靶点，以减轻与复发性流产相关的高身体，心理和经济负担。该项目利用了Brosens实验室的独特资源，包括获得新鲜子宫内膜组织和生物库样本（>5000）;获得导致植入失败，流产或活产的IVF胚胎的废培养基;和单细胞转录组数据（包括空间转录组学）对35例子宫内膜活检进行了研究，这些子宫内膜活检是在植入窗口期从既往有或无生殖失败的患者中获得的。此外，奥特教授将提供复杂的大型数据集分析的专业知识。

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.