Analysis of genome organization using computational approaches

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Project Description

The very long, linear DNA molecules that carry inheritable and instructive information in their nucleotide sequence need to be packed to fit into the nucleus of a cell. While it was initially thought that the organization that is accomplished by complexing DNA with histone proteins into chromatin and chromosomes constitutes mostly an inert scaffold, it is now becoming clear that the 3D organization of genomes is critical for organismal development, tissue homeostasis and reprogramming. Indeed, changes in genome architecture contribute to or are potentially causative of many diseases including degenerative, metabolic disorders and cancer. In consequence, insights into the architecture and regulation of 3D genome organization are expected to provide new concepts for disease diagnosis and therapy. While considerable progress has been made in the understanding of topologically associated domains (TADs) as fundamental elements of 3D genomes, very little is known about the formation, architecture and function of compartments as higher order principles of chromatin organization. Eu- and heterochromatin constitute elementary levels of genome compartmentalization and these are marked by different patterns of chromatin modifications. In particular, the prototypic histone H3K9me3 modification is generally correlated to heterochromatin in different experimental systems. Proteins of the heterochromatin protein 1 (HP1) family specifically recognize H3K9me3 and are thought to be crucial for mediating the function of the chromatin modification. We have generated genetic model systems in the nematode C. elegans to analyze the different components of (hetero-) chromatin) organization. Using different high throughput approaches (HiC, SPRITE, imaging) we are analyzing different mutant C. elegans clones. The current project targets the analysis of different next generation sequencing data using already established as well as novel bioinformatics pipelines. The work will be done in close interaction with (bio-)informaticians and biologists, thereby providing a stimulation, multidisciplinary research environment.
Program - BioScience
Division - Biological and Environmental Sciences and Engineering
Field of Study - Epigenetics

About the
Researcher

Wolfgang Fischle

Wolfgang Fischle

Desired Project Deliverables

  • Developing and adopting code for the analysis of HiC and SPRITE data using established pipelines (interaction frequency, modeling of 1D data into 2D and 3D)
  • Analysis of existing and future datasets of C. elegans mutants and in comparison to wild type
  • Synchronization of data analysis pipelines
  • Debugging of code
  • Documentation of analysis pipelines using GitHub and similar internal pipelines

RECOMMENDED STUDENT ACADEMIC & RESEARCH BACKGROUND

(bio-)informatics
(bio-)informatics
computational biology
computational biology
programming
programming