Ibrahim Cissé 生物物理学家

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Ibrahim Cissé
Biological Physicist | Class of 2021
Developing microscopy tools to investigate the subcellular processes underlying genetic regulation and misfunction.


Portrait of Ibrahim Cissé

Title
Biological Physicist
Affiliation
Department of Biological Physics, Max Planck Institute of Immunobiology and Epigenetics
Location
Freiburg, Germany
Age
38 at time of award
Area of Focus
Biochemistry, Biophysics, and Structural Biology
Website
icisse.org
Social
Twitter
Published September 28, 2021
ABOUT IBRAHIM'S WORK
Ibrahim Cissé is a biological physicist developing single-molecule super-resolution microscopic imaging and applying it to the investigation of subcellular processes in live cells. Cissé’s imaging tools facilitate the study of transient, loosely joined groups of biomolecules at high spatial and temporal resolutions (that is, with minute detail and with very little time between each image captured). His investigations deepen our understanding of how gene regulation and expression produce proteins in cells.

The control over expression (or activation) of specific genes begins with the process of transcription, whereby the genetic information in a segment of DNA is copied into RNA molecules. For protein-coding genes, RNA polymerase II (Pol II) performs this transcription. Cissé modified an existing high-resolution imaging method, Photo-Activated Localization Microscopy (PALM), to record the fast dynamics of single molecules during transcription over time. The spatial and temporal resolution of his time-correlated PALM (tcPALM) showed that Pol II forms temporary clusters at specific gene sites. This dynamic clustering and dissolution over a period of seconds challenges previous descriptions of polymerase clusters as static and pre-assembled. To better understand the function of Pol II clustering in transcription, Cissé and colleagues developed a method of dual-color, single molecule super-resolution microscopy in living cells, in which one color marks the enzyme Pol II and the other indicates RNA transcripts. They discovered that the duration of a Pol II cluster correlates with—in fact, predicts—the number of mRNA (messenger RNA transcripts) molecules that are subsequently synthesized. This clustering may provide insights into chromatin architecture (the 3D structure of genetic material inside the cell) and how that architecture is involved in packing distant DNA sequences close together for the dynamic regulation of gene expression. Cissé also demonstrated that Pol II clusters have all the defining hallmarks of biomolecular condensates that form via liquid-liquid phase separation—that is, liquid parts of a cell that do not have membrane barriers but can form distinct structures, similar to oil separating from water. Biological liquid-liquid phase separation has been the subject of much research in recent years due to discoveries indicating that biological condensates are part of many cell functions.

Cissé continues to push the limits of quantitative microscopy (a microscopic study that uses algorithmic analysis of digital images) in his efforts to further describe the physical mechanisms that condense and dissolve Pol II clusters and the chemical and biological processes underlying cells’ control of condensation. He is also advancing imaging methods to investigate the early stages of misfolded protein clustering, which may be critical to understanding neurodegenerative diseases such as Parkinson’s. His work revealed that the initial formation of misfolded protein clusters is akin to phase transitions that lead to condensates. Through his cutting-edge innovations in single-molecule microscopy and in-depth understanding of biophysical and cellular processes, Cissé is illuminating the dynamics of gene regulation and enabling further investigation of biological condensates.

BIOGRAPHY
Ibrahim Cissé received a BS (2004) from North Carolina Central University and a PhD (2009) from the University of Illinois at Urbana-Champaign. He served as a postdoctoral fellow at École Normale Supérieure de Paris from 2010 to 2012. Cissé was an assistant professor of physics and biology at the Massachusetts Institute of Technology beginning in 2014, and he was tenured in 2020. He was a professor of physics at the California Institute of Technology in 2021 prior to taking up his current position as director of the Department of Biological Physics at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, Germany. Cissé’s work has appeared in Nature, Science, Cell, and PNAS, among other scientific journals.



Ibrahim Cissé
生物物理学家｜2021级
开发显微镜工具，研究遗传调节和功能失调的亚细胞过程。


易卜拉欣-西塞的画像

标题
生物物理学家
工作单位
马克斯-普朗克免疫生物学和表观遗传学研究所生物物理系
工作地点
德国弗莱堡
年龄
获奖时38岁
重点领域
生物化学、生物物理学和结构生物学
网站
icisse.org
社会
推特
发表于2021年9月28日
关于易卜拉欣的工作
易卜拉欣-西塞是一位生物物理学家，他正在开发单分子超分辨率显微镜成像，并将其应用于活细胞中亚细胞过程的调查。Cissé的成像工具有助于在高空间和时间分辨率下研究瞬时的、松散连接的生物分子组（也就是说，具有微小的细节，并且每张图像的拍摄时间间隔非常短）。他的调查加深了我们对基因调控和表达如何在细胞中产生蛋白质的理解。

对特定基因的表达（或激活）的控制始于转录过程，即把一段DNA中的遗传信息复制成RNA分子。对于编码蛋白质的基因，RNA聚合酶II（Pol II）执行这种转录。Cissé修改了现有的高分辨率成像方法，即光激活定位显微镜（PALM），以记录单分子在转录过程中的快速动态变化。他的时间相关PALM（tcPALM）的空间和时间分辨率显示，Pol II在特定的基因位点形成了临时集群。这种在几秒钟内的动态集群和解体挑战了以前关于聚合酶集群是静态和预组装的描述。为了更好地了解Pol II集群在转录中的功能，Cissé及其同事开发了一种在活细胞中进行双色、单分子超分辨率显微镜观察的方法，其中一种颜色标志着Pol II酶，另一种则表示RNA转录物。他们发现Pol II集群的持续时间与随后合成的mRNA（信使RNA转录物）分子的数量相关--事实上是预测的。这种集群可能提供了对染色质结构（细胞内遗传物质的三维结构）的见解，以及该结构如何参与将遥远的DNA序列紧密地包装在一起以动态调节基因表达。Cissé还证明了Pol II集群具有通过液-液相分离形成的生物分子凝聚物的所有决定性特征--即细胞的液体部分没有膜屏障，但可以形成不同的结构，类似于油从水中分离。近年来，由于有发现表明生物液相分离是许多细胞功能的一部分，生物液相分离一直是许多研究的主题。

Cissé继续推动定量显微镜（一种使用数字图像的算法分析的显微镜研究）的极限，努力进一步描述凝聚和溶解Pol II集群的物理机制以及细胞控制凝聚的化学和生物过程。他还在推进成像方法，研究错误折叠蛋白集群的早期阶段，这可能对理解帕金森症等神经退行性疾病至关重要。他的工作显示，错误折叠的蛋白质集群的最初形成类似于导致冷凝物的相变。通过他在单分子显微镜方面的尖端创新以及对生物物理和细胞过程的深入理解，西塞正在阐明基因调控的动态，并使人们能够进一步研究生物凝集物。

个人简历
Ibrahim Cissé在北卡罗来纳中央大学获得学士学位（2004年），在伊利诺伊大学厄巴纳-香槟分校获得博士学位（2009年）。2010年至2012年，他在巴黎高等师范学院担任博士后研究人员。Cissé从2014年开始在麻省理工学院担任物理学和生物学助理教授，他在2020年获得终身职位。2021年，他在加州理工学院担任物理学教授，之后在德国弗莱堡的马克斯-普朗克免疫生物学和表观遗传学研究所担任生物物理学系主任的现职。Cissé的工作出现在《自然》、《科学》、《细胞》和《PNAS》等科学期刊上。