High-Resolution Functional Genomics Group

Dr. Andreas Mayer

September 28, 2020

If you want to apply your analytical and experimental skills to determine the key regulatory principles that underlie genome transcription and chromatin regulation in differentiated human cells and during cell differentiation, send your application materials to the IMPRS-BAC and join the Max Planck Research Group of Andreas Mayer.

Our research aims at the understanding of the key regulatory principles that drive genome transcription in mature mammalian cells and during cell differentiation. We are especially interested in how nascent transcription by RNA polymerase II (Pol II) is regulated in a dynamic chromatin environment in living cells. We are also interested in how a dysregulation of genome transcription causes human diseases such as neurodevelopmental disorders. To address these questions, we are developing and applying new quantitative genome-wide approaches in combination with computational analysis tools. For a more general description of our research please read this recent article highlighting our research or our previous review.

Sample Ph.D. project 1:

Our knowledge of the regulatory crosstalk between RNA polymerase II (Pol II) transcription and chromatin organization to control cell function is still incomplete. In this project, we aim to uncover molecular mechanisms that link Pol II transcription and chromatin organization. We will focus on the function of BET bromodomain proteins that act at the interface between genome transcription and chromatin regulation. The human BET protein family consists of BRD2, BRD3, BRD4 and BRDT. Its most prominent member BRD4 has been implicated in the regulation of Pol II transcription (Winter, Mayer et al., Mol Cell, 2017) and is emerging as a therapeutic target in a range of human diseases. We plan to study the functions of BET proteins in different human cellular models and during stem cell differentiation. We will use induced protein degradation to selectively impair BET protein function at high kinetic resolution in human cells. These analyses will be complemented by an interdisciplinary combination of quantitative genome- and proteome-wide approaches, genome engineering techniques (CRISPR/Cas9) and computational tools to reveal direct functions of BET proteins in transcription regulation and chromatin organization.

In case of interest, please visit the website of the Mayer Group.

Sample Ph.D. project 2:

Stem cell differentiation is driven by dynamic changes in gene transcription programs ultimately leading to cell type-specific gene expression landscapes. Notably, the pattern of alternative splicing, the fundamental process that generates different transcript isoforms from the same gene, also changes dramatically as cells differentiate into more specialized cells such as neurons. Changes in transcript isoforms can alter the function of the encoded protein. The molecular mechanisms that control these transcript isoform changes and its role in cell lineage determination are unclear. In this project we will identify and characterize transcript isoform changes during stem cell differentiation using different human cell differentiation models including a neuronal model. We will investigate the causes and consequences of alternative splicing for cell differentiation using a combined computational and experimental approach. We will perform time-course experiments to reveal the dynamical changes in transcript levels and identities, and in nascent transcription throughout the differentiation process using quantitative and high-resolution genome-wide approaches. An integrative computational analysis will then be performed to model and predict cell fate commitment.

In case of interest, please visit the website of the Mayer Group.

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