Obtaining a molecular understanding of antibody secretion

获得对抗体分泌的分子理解

• 批准号: BB/L022389/1
• 负责人: Andrew Peden
• 金额: $ 45.71万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FL022389%2F1
• 关键词: Obtaining; molecular; understanding; antibody; secretion

Constitutive secretion is the process by which cells deliver newly made protein to their outside. Cells can secrete a variety of different proteins and the most biologically and clinically important ones include collagen, cytokines and antibodies. Constitutive secretion is key to both normal heath and wellbeing as well as the manufacture of certain medicines such as therapeutic antibodies. Surprisingly, our understanding of this important process remains poor. This lack of basic knowledge will not only hinder improvements in the manufacturing of new drugs but also the development of novel medicines for the treatment of secretory-based diseases. My laboratory is interested in discovering the cellular machinery required for secretion. We are identifying this machinery by comparing cells which have high levels of secretion to those which do not using a technique called mass-spectrometry which allows the abundance of proteins to be measured. Our hypothesis is that cells which are actively involved in secretion should have more of the machinery required for performing this process. The cells we are comparing for these studies are B-cells and plasma cells. Plasma cells are the antibody producing cells of the immune system and they are capable of making and secreting hundreds of millions of antibodies per day while B-cells do not secrete any antibodies. Our pilot studies have identified several new factors which we believe are involved in secretion so indicating that a more comprehensive study is warranted. Once we have identified this novel secretory machinery will then work out how these proteins function by removing them from plasma cells using a technique called RNAi and determining whether the cells can still secrete antibodies. The knowledge generated from our research will benefit society because it will increase our understanding of a fundamental cellular process and in the future may help in the development of new manufacturing processes for therapeutic antibody production, tests for diagnosing disease and developing novel medicines for targeting diseases caused by inappropriate secretion.

组成性分泌是细胞将新产生的蛋白质输送到外部的过程。细胞可以分泌各种不同的蛋白质，最具生物学和临床意义的蛋白质包括胶原蛋白、细胞因子和抗体。组成性分泌是正常健康和福祉以及某些药物（如治疗性抗体）制造的关键。令人惊讶的是，我们对这一重要过程的理解仍然很差。缺乏基本知识不仅会阻碍新药生产的改进，而且会阻碍治疗分泌性疾病的新药的开发。我的实验室对发现分泌所需的细胞机制很感兴趣。我们正在通过比较具有高水平分泌的细胞和那些不使用质谱技术的细胞来识别这种机制，该技术允许测量蛋白质的丰度。我们的假设是，积极参与分泌的细胞应该有更多的执行这一过程所需的机制。我们在这些研究中比较的细胞是B细胞和浆细胞。浆细胞是免疫系统的抗体产生细胞，它们每天能够产生和分泌数亿种抗体，而B细胞不分泌任何抗体。我们的初步研究已经确定了几个新的因素，我们认为这些因素与分泌有关，这表明需要进行更全面的研究。一旦我们确定了这种新的分泌机制，我们将通过使用一种称为RNAi的技术将这些蛋白质从浆细胞中去除并确定细胞是否仍然可以分泌抗体来研究这些蛋白质的功能。从我们的研究中产生的知识将有益于社会，因为它将增加我们对基本细胞过程的理解，并在未来可能有助于开发新的治疗性抗体生产制造工艺，诊断疾病的测试和开发针对由不适当分泌引起的疾病的新药。

项目成果

Sec22b is a critical and nonredundant regulator of plasma cell maintenance.

• DOI: 10.1073/pnas.2213056120
• 发表时间: 2023-01-10
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1

Plasma cell maintenance and antibody secretion are under the control of Sec22b-mediated regulation of organelle dynamics

• DOI: 10.1101/2022.01.14.476154
• 发表时间: 2022-01
• 期刊: bioRxiv
• 作者: A. Bonaud;Laetitia Gargowitsch;S. Gilbert;E. Rajan;Pablo Canales Herrerias;D. Stockholm;Nabila Rahman;M. Collins;D. Hill;Andrés Alloatti;Nagham Alouche;Stéphanie Balor;Vanessa Soldan;D. Gillet;J. Barbier;F. Bachelerie;Kenneth G. C. Smith;P. Bruhns;S. Amigorena;K. Balabanian;M. Linterman;A. Peden;M. Espéli

The SNARE VAMP7 Regulates Exocytic Trafficking of Interleukin-12 in Dendritic Cells.

SNARE VAMP7调节了树突状细胞中白细胞介素12的胞外运输。

• DOI: 10.1016/j.celrep.2016.02.055
• 发表时间: 2016-03-22
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Chiaruttini G;Piperno GM;Jouve M;De Nardi F;Larghi P;Peden AA;Baj G;Müller S;Valitutti S;Galli T;Benvenuti F
• 通讯作者: Benvenuti F