英国博士招聘-伦敦帝国理工学院-3D染色质组织及其发展时的调控作用

发布时间：2020-11-20

浏览次数：844次

如有招聘信息发布(博士/博后/访学)可联系

邮箱：cxw@med.tj.cn

微信：shelver888

公众号链接：https://mp.weixin.qq.com/s?__biz=MzU5NTk2OTE2Mw==&mid=2247485838&idx=1&sn=7310d24588e5f46bd989797ec1da506d&chksm=fe689c6ac91f157cb3ce82bf9f909eb367bf10031daea952f8ad61aa7332c392fd05380849d1&token=1134891688&lang=zh_CN#rd

学校：伦敦帝国理工学院

院系：MRC London Institute of Medical Sciences (LMS)

教授：Dr J Vaquerizas

申请网址：https://www.applysquare.com/opportunity-cn/o9yicHTLc7QR9/

截止日期：December 15, 2020

介绍

染色质在相间核中的三维组织对于基因表达的正确调节起着至关重要的作用（1）人体中几乎所有细胞都有2米的DNA，需要将其封装在原子核的物理空间（几微米）内，同时确保使您的细胞正常工作的调节机制能够做到这一点。当您想在一个盒子里放一个对您来说稀有的东西的盒子时，这有点像将家具存放在一个储存容器中–类似地，细胞需要确保它们在正确的时间访问关键的遗传信息。这个组织非常重要，因为当它被破坏时，会导致发育障碍和癌症（2）在过去的几年中，我们和其他人揭示了基因组如何在细胞核的3D空间中编排的关键原理，从果蝇到哺乳动物（3-7）特别是，我们专注于尝试了解早期胚胎发育过程中的关键发育阶段，例如合子基因组的激活和表观遗传程序发生重大变化的细胞命运的建立（8）但是，尽管取得了这些进展，但我们仍然对这些分子机制如何发挥作用以及它们在调节基因表达中的作用缺乏基本的了解。

当前项目的目的是破译协调基因组三维组织的分子机制，以及它们对建立细胞命运的贡献。为了实现这一目标，该项目结合了使用不同遗传系统生成最新基因组学数据集（例如Hi-C，单细胞RNA-seq，CUT＆TAG）以及使用先进的计算方法进行分析的能力并整合它们。总体而言，该项目将帮助您了解3D基因组的工作原理，并为您提供有关现代分子生物学和计算技术的全面培训。先前的计算经验不是先决条件，而是对计算工作的强烈偏爱，以及敏锐的分析头脑将是一个强大的优势。

资金说明

医学研究理事会提供3.5年的全额奖学金。

这项奖学金涵盖了伦敦帝国学院的所有学费，并直接向学生支付了每年21,000英镑（每月分期付款）的津贴。

参考文献

1. R. Stadhouders, G. J. Filion, T. Graf, Transcription factors and 3D genome conformation in cell-fate decisions. Nature. 569, 345–354 (2019). 

2. M. Spielmann, D. G. Lupiáñez, S. Mundlos, Structural variation in the 3D genome. Nat. Rev. Genet. 19, 453–467 (2018). 

3. C. B. Hug, A. G. Grimaldi, K. Kruse, J. M. Vaquerizas, Chromatin Architecture Emerges during Zygotic Genome Activation Independent of Transcription. Cell. 169, 216-228.e19 (2017). 

4. J. D. P. Rhodes, A. Feldmann, B. Hernández-Rodríguez, N. Díaz, J. M. Brown, N. A. Fursova, N. P. Blackledge, P. Prathapan, P. Dobrinic, M. K. Huseyin, A. Szczurek, K. Kruse, K. A. Nasmyth, V. J. Buckle, J. M. Vaquerizas, R. J. Klose, Cohesin Disrupts Polycomb-Dependent Chromosome Interactions in Embryonic Stem Cells. Cell Rep. 30, 820-835.e10 (2020). 

5. K. Kruse, N. Diaz, R. Enriquez-Gasca, X. Gaume, M.-E. Torres-Padilla, J. M. Vaquerizas, Transposable elements drive reorganisation of 3D chromatin during early embryogenesis. bioRxiv, 523712 (2019). 

6. N. Díaz, K. Kruse, T. Erdmann, A. M. Staiger, G. Ott, G. Lenz, J. M. Vaquerizas, Chromatin conformation analysis of primary patient tissue using a low input Hi-C method. Nat. Commun. 9, 4938 (2018). 

7. E. Ing-Simmons, R. Vaid, M. Mannervik, J. M. Vaquerizas, bioRxiv, doi:10.1101/2020.07.07.186791. 

8. C. B. Hug, J. M. Vaquerizas, The Birth of the 3D Genome during Early Embryonic Development. Trends Genet. 34, 903–914 (2018). 

申请

https://www.applysquare.com/opportunity-cn/o9yicHTLc7QR9/

Job description

About the Project

The three-dimensional organisation of chromatin in the interphase nucleus plays a crucial role for the correct regulation of gene expression (1). Almost all cells in your body have 2 metres of DNA that need to be encapsulated within the physical space of the nucleus, a few microns, while making sure that the regulatory mechanisms that allow your cells to work properly do so. It’s a little bit like storing furniture inside a storage container when you want to find that box inside a box that has this little thing precious to you – similarly, cells needs to ensure that they have access to key genetic information at the right time. This organisation is very important because when it is disrupted, it leads to developmental disorders and cancer (2). 

In the last few years we and others have unveiled key principles of how the genome is organised in the 3D space of the nucleus in species ranging from fruit flies to mammals (3–7). In particular, we have focused on trying to understand key developmental stages during early embryonic development, such as the activation of the zygotic genome and the establishment of cellular fates, where major changes in epigenetic programmes occur (8). However, despite these advances, we still lack a fundamental understanding of how these molecular mechanisms work and their effect in regulating gene expression. 

The goal of the current project is to decipher molecular mechanisms by which the three-dimensional organisation of the genome is orchestrated, and their contribution to the establishment of cellular fate. To achieve this goal, this project combines the generation of state-of-the-art genomics datasets (e.g., Hi-C, single-cell RNA-seq, CUT&TAG) using different genetic systems, and the usage of advanced computational approaches to analyse and integrate them. Overall, this project will help understand how the 3D genome works and will give you comprehensive training in modern molecular biology and computational techniques. Previous computational experience is not a pre-requisite, but a strong inclination towards computational work, and a crisp analytical mind will be a strong advantage. 

Funding Notes

This is a fully-funded 3.5 year studentship funded by the Medical Research Council. 

The studentship covers all tuition fees with Imperial College London and stipend payments amounting to £21,000pa (paid in monthly instalments) directly to the student. 

References

1. R. Stadhouders, G. J. Filion, T. Graf, Transcription factors and 3D genome conformation in cell-fate decisions. Nature. 569, 345–354 (2019). 

2. M. Spielmann, D. G. Lupiáñez, S. Mundlos, Structural variation in the 3D genome. Nat. Rev. Genet. 19, 453–467 (2018). 

3. C. B. Hug, A. G. Grimaldi, K. Kruse, J. M. Vaquerizas, Chromatin Architecture Emerges during Zygotic Genome Activation Independent of Transcription. Cell. 169, 216-228.e19 (2017). 

4. J. D. P. Rhodes, A. Feldmann, B. Hernández-Rodríguez, N. Díaz, J. M. Brown, N. A. Fursova, N. P. Blackledge, P. Prathapan, P. Dobrinic, M. K. Huseyin, A. Szczurek, K. Kruse, K. A. Nasmyth, V. J. Buckle, J. M. Vaquerizas, R. J. Klose, Cohesin Disrupts Polycomb-Dependent Chromosome Interactions in Embryonic Stem Cells. Cell Rep. 30, 820-835.e10 (2020). 

5. K. Kruse, N. Diaz, R. Enriquez-Gasca, X. Gaume, M.-E. Torres-Padilla, J. M. Vaquerizas, Transposable elements drive reorganisation of 3D chromatin during early embryogenesis. bioRxiv, 523712 (2019). 

6. N. Díaz, K. Kruse, T. Erdmann, A. M. Staiger, G. Ott, G. Lenz, J. M. Vaquerizas, Chromatin conformation analysis of primary patient tissue using a low input Hi-C method. Nat. Commun. 9, 4938 (2018). 

7. E. Ing-Simmons, R. Vaid, M. Mannervik, J. M. Vaquerizas, bioRxiv, doi:10.1101/2020.07.07.186791. 

8. C. B. Hug, J. M. Vaquerizas, The Birth of the 3D Genome during Early Embryonic Development. Trends Genet. 34, 903–914 (2018). 

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