Correlative super-resolution light and X-ray microscopy to probe genome organisation

Supervisor Organisation PhD Awarding Entity: phd location
Heidelberg University
Heidelberg University
Heidelberg, Germany

Research Focus

Chromatin organization plays an important role in the regulation and maintenance of genes in the normal biological process and in response to environment.

The disruption of the organization of chromatin has a significant impact on many cell processes, often associated with many pathological processes such as aging and cancer. Recent advances in microscopy techniques open up new opportunities to directly visualize higher-order chromatin architecture, its compaction status and its functional states at nanometer resolution in the intact cells or tissue.

The project aims to develop correlative imaging based on super resolution fluorescence and soft x-ray microscopies in 3D via full-field rotation. Such full-field rotation will enable structural and functional studies to probe chromatin architecture in key cellular processes at nanometer resolution in 3D.

Full-rotation, tomographic imaging is the unique way to obtain 3D cell structure with isotropic resolution. While means for full-rotation soft x-ray tomography are established, super-resolution techniques are typically limited to 2D information or confocal geometry. This project focuses on development of axial super-resolution microscopy which is compatible with thin glass-wall capillaries used in soft x-ray tomography.

Methodology

Full-rotation, tomographic imaging is the unique way to obtain 3D cell structure with isotropic resolution. While means for full-rotation soft x-ray tomography are established, super-resolution techniques are typically limited to 2D information or confocal geometry. This project focuses on development of axial super-resolution microscopy which is compatible with thin glass-wall capillaries used in soft x-ray tomography.

Aim 1

Development of axial super-resolution microscopy on thin glass-wall capillaries, including sample preparation, image acquisition and plunge freezing.

Aim 2

Development of fiducial markers and volume analysis pipelines to correlate soft x-ray tomography and super-resolution microscopy.

Aim 3

3D mapping of chromatin compaction by means of correlative approach to understand formation of memory in brain cells.

Pictures Attached

3D Distribution of hetero- and eu-chromation by SXT

PhD Researcher

Name: Fariha Mahzabin Annesha

University: University of Heidelberg

Supervisor’s Name: Dr. Venera Weinhardt/ Prof Joachim Wittbrodt

Fariha Mahzabin Annesha completed her bachelor’s in Biomedical Engineering at the Military Institute of Science and Technology, Bangladesh. Later, she went on to pursue a master’s degree in Biomedical Imaging at the University of Turku, Finland, where she delved into the integration of engineering principles with advanced imaging techniques. Her master’s thesis was done in collaboration with TissueGnostics GmbH, Austria which focused on developing a framework for systematic comparison of cell segmentation algorithms in histopathological images. Before starting her PhD studies, Fariha was a Research Assistant at the University of Turku in the Bioimage-informatics group where she worked on improving an algorithm for detecting and classifying overlapping cell and tissue annotations through the development of whole-slide-image (WSI) registration algorithms.

Her PhD project revolves around correlating super-resolution fluorescence and soft x-ray microscopies in a 3D context through full-field rotation. The groundbreaking potential lies in obtaining nanometer-resolution insights into chromatin architecture within the nucleus during crucial cellular processes. Unlike typical super-resolution techniques limited to 2D or confocal geometry, this project uniquely concentrates on advancing axial super-resolution microscopy compatible with the thin glass-wall capillaries utilized in soft X-ray tomography. Additionally, the project aims to develop fiducial markers and sophisticated volume analysis pipelines to correlate data between soft X-ray tomography and super-resolution microscopy.

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