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

我们身体的每个细胞表面都有糖，即所谓的聚糖，它们与其他生物分子（如蛋白质）相连。当一个细胞变成癌细胞时，它会显示出帮助癌细胞存活的不同类型的糖蛋白。目前，英国国家医疗服务体系用于检测癌症的一些生物标志物是含有大量聚糖的蛋白质。虽然肿瘤糖蛋白在诊断和治疗方面具有突出的临床潜力，但仅通过生物学方法将其与宿主体内的天然糖蛋白区分开来是非常具有挑战性的。通过我们小组的突破性新进展（Nat. common . 2022； J. Proteom. 2021; Nature 2019;），这些工具最终可以准确地描述癌症衍生糖蛋白，并了解它们在肿瘤发生过程中如何变化，例如被宿主来源的细胞包围或转移时。在此学习期间，您将在离体细胞生物学（Cancer Lett. 2022; Nat. Protoc. 2020），化学生物学（Nat. common . 2022; Curr. c. 2022）中应用创新工具。当今。化学。质谱（glyco-）蛋白质组学（J. Proteom. 2018）； Dis. Model and Mech. 2020；Soc。以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。在与所有三个小组的成员密切合作中，您将使用这些工具来了解宿主细胞的存在如何“塑造”这些糖蛋白的特征。该项目建立在所有三个实验室之前的工作基础上，并将重点放在体外组织共培养以及质谱糖蛋白组分析上。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，在研究的各个方面都有出色的强大支持，包括最先进的蛋白质组学科学技术平台（STP）。在克里克，你将由Ben Schumann博士和Ilaria Malanchi博士共同指导，与顶级癌症研究所Paul Huang博士的实验室关系密切。你将与所有三个小组的实验室成员以及stp一起工作。我们正在寻找具有生物学，生物化学，化学生物学或相关领域的优秀背景的候选人。有哺乳动物细胞培养和/或质谱蛋白质组学经验者优先，并有机会在高度支持的环境中进行培训。我们非常重视良好的沟通技巧、团队合作、科学诚信以及对健康和安全各个方面的关注。您将被纳入帝国理工学院化学系化学生物学研究所博士课程，该课程具有出色的支持，定期进度报告和评估。这个项目不需要合成化学方面的经验或背景。请注意，本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 et al.， J. Amer。Soc。质谱。32,2021。乔思等人，《中华人民共和国学报》第13期，2022年。柯尔等人。当今。化学。生物工程学报，2016。陈建军，陈建军，陈建军，等。Krasny等人，Dis. Model and Mech. 13, 2020。李建军，李建军，李建军，等。Ombrato等人，Nature 572, 2019。Ombrato et al.， Nat协议16,2020。Rosell et al.，癌症杂志，544,2022。

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.