A Molecular Magnifying Glass to Dissect the Interaction Between Cancer and Host

我们体内的每个细胞表面都有糖，也就是所谓的葡聚糖，它们与蛋白质等其他生物分子相连。当细胞转变为癌细胞时，它会显示不同类型的糖蛋白，帮助癌症存活。NHS目前用来检测癌症的一些生物标记物是含有非常高数量的糖链的蛋白质。虽然癌症糖蛋白在临床诊断和治疗方面具有巨大的潜力，但仅从生物学的角度来区分它们与宿主的天然糖蛋白是非常具有挑战性的。通过我们集团的突破性新发展(NAT。交警。2022年；J.Proteom。2021；自然2019；)这些工具终于触手可及，可以准确地描绘癌症衍生的糖蛋白，并了解它们在肿瘤发生过程中的变化，例如当被宿主衍生细胞包围时或在转移中。在这一学习中，你将在体外细胞生物学(癌症Lett)中应用创新工具。2022；NAT。普罗托克。2020)、化学生物学(NAT.交警。2022年；货币奥平。化学。比奥尔。2021)和质谱学(糖)蛋白质组学(J.Proteom.2018年；Dis.模特和机甲。2020年；J·阿梅尔。SoC。质谱学。2021)研究乳腺癌细胞特异性产生的糖蛋白及其在疾病形成中的作用。在与所有三个小组成员的密切合作中，您将使用这些工具来了解宿主细胞的存在如何“塑造”这些糖蛋白的签名。该项目建立在所有三个实验室先前工作的基础上，将重点放在体外组织共培养以及质谱糖蛋白质组分析上。该项目将以弗朗西斯·克里克研究所为基础，该研究所是生物医学科学的旗舰机构，在包括最先进的蛋白质组学科学技术平台(STP)在内的所有研究方面都得到了强有力的支持。在克里克，你将由本·舒曼博士和伊拉里亚·马兰奇博士共同监督，并与顶级癌症研究所的保罗·黄博士的实验室建立密切关系。您将与所有三个小组的实验成员以及STP一起工作。我们正在寻找具有生物、生物化学、化学生物学或相关领域优秀背景的候选人。有哺乳动物细胞培养和/或质谱学蛋白质组学经验者优先，并有在高度支持性环境中的培训机会。我们非常重视沟通能力、团队合作精神、科学诚信以及对健康和安全的方方面面的关注。你将被纳入帝国理工学院化学系化学生物学研究所的博士课程，以出色的支持、定期的进展报告和评估为特色。这个项目不需要在合成化学方面的经验或背景。请注意，这个项目可能需要使用来自实验动物的细胞或组织。不需要直接的动物工作。参考文献：Calle等人，J.Amer。SoC。质谱学。32,2021.Cioce等人，NAT.交警。2022年12月13日Cioce等人，Curr.奥平。化学。比奥尔。60,2021.Krasny等人，J.Proteom.189,2018.Krasny等人，Dis.模特和机甲。13,2020.Milighetti等人，J.Proteom。241.2021.Ombrato等人，自然572,2019.Ombrato等人，NAT.普罗托克。16,2020.Rosell等人，癌症Lett。544,2022年。

Every cell in our body displays on the surface sugars, so-called glycans, that are linked to other biomolecules such as proteins. When a cell turns into a cancer cell, it displays different types of glycoproteins that help the cancer survive. Some of the current biomarkers used by the NHS to detect cancer are proteins that contain very high amounts of glycans. While cancer glycoproteins have outstanding clinical potential for both diagnosis and therapy, it is very challenging to distinguish them from native glycoproteins from the host by methods of biology alone. Through ground-breaking new developments in our groups (Nat. Commun. 2022; J. Proteom. 2021; Nature 2019;) the tools are finally within reach to accurately profile cancer-derived glycoproteins and understand how they change during tumorigenesis, for instance when surrounded by host-derived cells or in metastasis.In this studentship, you will apply innovative tools in ex vivo cell biology (Cancer Lett. 2022; Nat. Protoc. 2020), chemical biology (Nat. Commun. 2022; Curr. Opin. Chem. Biol. 2021) and mass spectrometry (glyco-)proteomics (J. Proteom. 2018; Dis. Model and Mech. 2020; J. Amer. Soc. Mass Spectrom. 2021) to study the glycoproteins specifically produced by breast cancer cells, and their role in disease formation. In close collaboration with members of all three groups, you will use these tools to understand how the presence of host cells "shapes" the signature of these glycoproteins. The project builds on prior work of all three labs and will focus on ex vivo tissue co-culture as well as mass spectrometry glycoproteome analysis.This project will be based at the Francis Crick Institute, a flagship of biomedical science with outstanding strong support in all aspects of research including a state-of-the-art Proteomics Science Technology Platform (STP). At the Crick, you will be jointly supervised by Dr. Ben Schumann and Dr. Ilaria Malanchi, with close relationships with the lab of Dr. Paul Huang at the top-tier Institute of Cancer Research. You will work with lab members of all three groups as well as the STPs. We are looking for candidates with an excellent background in biology, biochemistry, chemical biology or related fields. Experience in mammalian cell culture and/or mass spectrometry proteomics is desirable, with training opportunities in a highly supportive environment. We put heavy emphasis on strong communication skills, collegiality, scientific integrity and mindfulness of all aspects of health and safety. You will be integrated in the Institute of Chemical Biology PhD programme at the Imperial College Chemistry Department of Chemistry, featuring outstanding support, regular progress reports and assessments. This project requires no experience or background in synthetic chemistry. Please note that this project might require working with cells or tissues derived from laboratory animals. Direct animal work is not required. References:Calle et al., J. Amer. Soc. Mass Spectrom. 32, 2021.Cioce et al., Nat. Commun. 13, 2022.Cioce et al., Curr. Opin. Chem. Biol. 60, 2021.Krasny et al., J. Proteom. 189, 2018.Krasny et al., Dis. Model and Mech. 13, 2020.Milighetti et al., J. Proteom. 241, 2021.Ombrato et al., Nature 572, 2019.Ombrato et al., Nat. Protoc. 16, 2020.Rosell et al., Cancer Lett. 544, 2022.