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Helmholtz Munich | Marlet Morales

Chromatin Dynamics and Epigenetics

Schneider Lab

About our Research

– Decoding and harnessing the power of epigenetics –

Our mission is to decipher the molecular mechanisms underlying epigenetic inheritance and epigenetic regulation of cellular function. We will develop novel solutions for environmentally triggered diseases and promote a healthier society in a rapidly changing world.

To accommodate the 2m of DNA into the small nucleus of our cells, it interacts with histone proteins forming a structure called chromatin. This chromatin can be dynamically altered through epigenetic mechanisms such as the addition of small chemical modifications. These modifications can then serve as ON or OFF switches for our genes encoded in the DNA. If well-coordinated, such epigenetic mechanisms enable our cells to quickly react to environmental changes and adapt DNA-templated processes e.g. gene expression, to cellular needs. However, when disturbed, these epigenetic processes can cause serious cellular abnormalities with fatal disease outcomes. By decoding and harnessing the power of epigenetics we will tackle epigenetic defects in cellular decision making, cancer and metabolic diseases and thus to prevent, cure or alleviate previously untreatable diseases.

Chromatin consists of a repeating array of its fundamental unit – the nucleosome. A nucleosome comprises 146 bp of DNA wrapped around a histone octamer (formed by two copies of the core histones H2A, H2B, H3, and H4) and histone H1 protecting the linker DNA between two nucleosomes. This linker histone H1 has an important function in establishing and maintaining chromatin organisation. Like the core histones, it can be highly covalently modified, however very little is known about the function of H1 modifications.

In addition to covalent modification, histone variants can regulate chromatin dependent processes. Histone H1 possesses many variants; up to 11 in mammalian cells. We are systematically investigating the biological function of H1 variants. We want to unravel: What is their role in epigenetic reprogramming, stem cell biology and disease progression ? Our research on H1 will transform the role of histone H1 variants from  mere structural chromatin components towards specific functions in cellular plasticity, reprogramming and diseases.

Chemical modifications of histone proteins emerged in the last decade as crucial players in regulating chromatin structure and as carriers of epigenetic information. The major challenges are now (i) to understand how these histone modifications are translated into concrete signals for e.g. turning genes ON and OFF and (ii) how our environment impacts histone modifications. We have discovered new types and sites of histone modifications on the histone tails and within the nucleosomal core. We identified novel mechanisms regulating chromatin function including causative roles for modifications within the core of the nucleosome.

We are now using novel approaches (including various types of “omics” with low or single cell input as well as in vitro approaches such as chromatin reconstitutions) to systematically unravel: How do novel types and sites of histone modifications mechanistically regulate chromatin function? and How can histone modifications couple chromatin structure and hence gene expression programs with cellular metabolism and metabolic diseases?  We will gain unique insights into novel mechanisms regulating cellular biology and predisposition for diseases through environmental impacts.

 

It is a key challenge for biologists to understand how chromatin regulates cellular processes at a single cell level and how these “epigenetic” states are inherited from one cell to it’s progenies.

To overcome this challenge, we implemented a novel microfluidics system. We develop and fabricate microfluidics devices that can “trap” individual cells within microchannels and allow us to monitor single cells over extended periods of time. This unique setup is empowering us to tackle key questions about epigenetic memory in single cells and epigenetic inheritance to their progenies. We can now investigate the inheritance of cellular components and transcriptional states over multiple. We will be able to (i) understand how cells adapt their transcriptional response to repeated environmental stimuli and how genes “remember” their previous transcriptional state as well as (ii) generate comprehensive data to model and predict the stochasticity of gene expression and its response to changing environments.

The emerging research field of ‘Epitranscriptomics’ tackles one of the next challenges for molecular biology: the understanding of how RNA modifications affect the function of RNAs and of their vital role in cellular biology. Such modifications of RNAs, most of them methylations, occur on all types of our RNAs. They are involved in the regulation of diverse biological processes. Misregulated RNA methyltransferases (the enzymes that add these modifications) have been found in multiple cancer types and are extremely promising targets for a new generation of anti-cancer drugs.

Leveraging our expertise on histone methylation we are now focusing on the identification of RNA methyltransferases, their biological function (in cells and full organisms), and the role of RNA methylation in cellular decision-making in individual cells. This will lay the foundations for the design of novel selective inhibitors for future therapeutic interventions.

Epigenetic information is “read” by epigenetic effector molecules that recognize DNA and histone modifications through specialized binding domains. Thereby, they can regulate chromatin function and orchestrate subsequent biological events. However, chromatin modifications do not act in isolation but form combinatorial modification signatures that define the functional state of the underlying chromatin. Consequently, epigenetic effectors need to be able to decode the encrypted message without any errors.

We study how epigenetic effector molecules can recognize and integrate multiple chromatin modification patterns in order to decipher the “epigenetic code”. Moreover, we want to unravel how these factors operate at the molecular level both in healthy and pathological conditions to aid in the development of epigenetic drugs for diseases caused by epigenetic defects.

(Supervised by Dr. Till Bartke)

Replication is the fundamental process that ensures that every cell within an organism contains the same hereditary information. Each cell has many origins of replication (ORIs), but not all of them are active. Moreover, cells, even if they are from the same cell type, can differ in their active ORIs. How a cell decides which ORI should be activated and how it coordinates their activation is still unclear. We investigate whether the nuclear DNA organization plays an important role in the selection of ORIs, and whether ORIs that are in close proximity to each other are activated together. 

Following DNA replication, epigenetic marks need to be re-established on the newly synthesized DNA strands. The protein UHRF1 plays a key role in coupling DNA methylation to DNA replication and it is misexpressed in many cancer types. We aim to unravel the molecular functions of UHRF1 in order to devise the development of drugs that target this important protein.

(Supervised by Dr. Till Bartke)

Chromatin consists of a repeating array of its fundamental unit – the nucleosome. A nucleosome comprises 146 bp of DNA wrapped around a histone octamer (formed by two copies of the core histones H2A, H2B, H3, and H4) and histone H1 protecting the linker DNA between two nucleosomes. This linker histone H1 has an important function in establishing and maintaining chromatin organisation. Like the core histones, it can be highly covalently modified, however very little is known about the function of H1 modifications.

In addition to covalent modification, histone variants can regulate chromatin dependent processes. Histone H1 possesses many variants; up to 11 in mammalian cells. We are systematically investigating the biological function of H1 variants. We want to unravel: What is their role in epigenetic reprogramming, stem cell biology and disease progression ? Our research on H1 will transform the role of histone H1 variants from  mere structural chromatin components towards specific functions in cellular plasticity, reprogramming and diseases.

Chemical modifications of histone proteins emerged in the last decade as crucial players in regulating chromatin structure and as carriers of epigenetic information. The major challenges are now (i) to understand how these histone modifications are translated into concrete signals for e.g. turning genes ON and OFF and (ii) how our environment impacts histone modifications. We have discovered new types and sites of histone modifications on the histone tails and within the nucleosomal core. We identified novel mechanisms regulating chromatin function including causative roles for modifications within the core of the nucleosome.

We are now using novel approaches (including various types of “omics” with low or single cell input as well as in vitro approaches such as chromatin reconstitutions) to systematically unravel: How do novel types and sites of histone modifications mechanistically regulate chromatin function? and How can histone modifications couple chromatin structure and hence gene expression programs with cellular metabolism and metabolic diseases?  We will gain unique insights into novel mechanisms regulating cellular biology and predisposition for diseases through environmental impacts.

 

It is a key challenge for biologists to understand how chromatin regulates cellular processes at a single cell level and how these “epigenetic” states are inherited from one cell to it’s progenies.

To overcome this challenge, we implemented a novel microfluidics system. We develop and fabricate microfluidics devices that can “trap” individual cells within microchannels and allow us to monitor single cells over extended periods of time. This unique setup is empowering us to tackle key questions about epigenetic memory in single cells and epigenetic inheritance to their progenies. We can now investigate the inheritance of cellular components and transcriptional states over multiple. We will be able to (i) understand how cells adapt their transcriptional response to repeated environmental stimuli and how genes “remember” their previous transcriptional state as well as (ii) generate comprehensive data to model and predict the stochasticity of gene expression and its response to changing environments.

The emerging research field of ‘Epitranscriptomics’ tackles one of the next challenges for molecular biology: the understanding of how RNA modifications affect the function of RNAs and of their vital role in cellular biology. Such modifications of RNAs, most of them methylations, occur on all types of our RNAs. They are involved in the regulation of diverse biological processes. Misregulated RNA methyltransferases (the enzymes that add these modifications) have been found in multiple cancer types and are extremely promising targets for a new generation of anti-cancer drugs.

Leveraging our expertise on histone methylation we are now focusing on the identification of RNA methyltransferases, their biological function (in cells and full organisms), and the role of RNA methylation in cellular decision-making in individual cells. This will lay the foundations for the design of novel selective inhibitors for future therapeutic interventions.

Epigenetic information is “read” by epigenetic effector molecules that recognize DNA and histone modifications through specialized binding domains. Thereby, they can regulate chromatin function and orchestrate subsequent biological events. However, chromatin modifications do not act in isolation but form combinatorial modification signatures that define the functional state of the underlying chromatin. Consequently, epigenetic effectors need to be able to decode the encrypted message without any errors.

We study how epigenetic effector molecules can recognize and integrate multiple chromatin modification patterns in order to decipher the “epigenetic code”. Moreover, we want to unravel how these factors operate at the molecular level both in healthy and pathological conditions to aid in the development of epigenetic drugs for diseases caused by epigenetic defects.

(Supervised by Dr. Till Bartke)

Replication is the fundamental process that ensures that every cell within an organism contains the same hereditary information. Each cell has many origins of replication (ORIs), but not all of them are active. Moreover, cells, even if they are from the same cell type, can differ in their active ORIs. How a cell decides which ORI should be activated and how it coordinates their activation is still unclear. We investigate whether the nuclear DNA organization plays an important role in the selection of ORIs, and whether ORIs that are in close proximity to each other are activated together. 

Following DNA replication, epigenetic marks need to be re-established on the newly synthesized DNA strands. The protein UHRF1 plays a key role in coupling DNA methylation to DNA replication and it is misexpressed in many cancer types. We aim to unravel the molecular functions of UHRF1 in order to devise the development of drugs that target this important protein.

(Supervised by Dr. Till Bartke)

The Schneider Lab

Prof. Robert Schneider

Director Functional Epigenetics

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Dr Till Bartke

Deputy Director of the Institute of Functional Epigenetics

Sandra Nitsch

Doctoral Researcher

Kevin Brockers

Doctoral Researcher

Palma Rico

Research Technician

Marlet Morales Franco

Doctoral Researcher

Simona Nasiscionyte

Doctoral Researcher

Dr. Amelie Johanna Kraus

Scientific Coordinator for Epigenetics

Amelie J. Kraus did her Master’s degree at the University of Würzburg. There, she got interested in Epigenetics and joined the Siegel's Lab for her PhD. She worked on the epigenetic gene regulation in the protozoan parasite Trypanosoma brucei. During her PhD, Amelie could gain experience in event and non-scientific project management. She joined the team in October 2019 as Scientific Coordinator for Epigenetics.

Nationality: German

Thomas Gerling

Administrative Assistant

Magdalena Valenta

PhD Student

Building 3526, Room 008

Dr. Andrey Tvardovskiy

Postdoc

Huiwen Li

Doctoral Researcher

Yu-Hao (Eric) Liu

Doctoral Researcher

Gabriela Santos

Bioinformatician

Dr. Jessica Pellegrino

Postdoc

Dr. Igor Kukhtevich

Postdoc

Bihter Özdemir Aygenli

Doctoral Researcher

Emilia Izabela Cepowska

Doctoral Researcher

Katharina Arnold

Doctoral Researcher

Recent Publications

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2022 Scientific Article in Nature Communications

Günsel, G.G.# ; Conlon, T.M.# ; Jeridi, A.# ; Kim, R. ; Ertüz, Z. ; Lang, N.J. ; Ansari, M. ; Novikova, M. ; Jiang, D. ; Strunz, M. ; Gaianova, M. ; Hollauer, C. ; Gabriel, C. ; Angelidis, I. ; Doll, S. ; Pestoni, J. ; Edelmann, S.L. ; Kohlhepp, M.S. ; Guillot, A. ; Bassler, K. ; Van Eeckhoutte, H.P. ; Kayalar, Ö. ; Konyalilar, N. ; Kanashova, T. ; Rodius, S. ; Ballester-Lopez, C. ; Genes Robles, C.M. ; Smirnova, N.F. ; Rehberg, M. ; Agarwal, C. ; Krikki, I. ; Piavaux, B. ; Verleden, S.E. ; Vanaudenaerde, B. ; Königshoff, M. ; Dittmar, G. ; Bracke, K.R. ; Schultze, J.L. ; Watz, H. ; Eickelberg, O. ; Stöger, T. ; Burgstaller, G. ; Tacke, F. ; Heissmeyer, V. ; Rinkevich, Y. ; Bayram, H. ; Schiller, H. B. ; Conrad, M. ; Schneider, R. ; Yildirim, A.Ö.

The arginine methyltransferase PRMT7 promotes extravasation of monocytes resulting in tissue injury in COPD.

2020 Scientific Article in Science Advances

Ignatova, V.V. ; Kaiser, S. ; Ho, J.S.Y. ; Bing, X. ; Stolz, P. ; Tan, Y.X. ; Lee, C.L. ; Gay, F.P.H. ; Lastres, P.R. ; Gerlini, R. ; Rathkolb, B. ; Aguilar-Pimentel, J.A. ; Sanz-Moreno, A. ; Klein-Rodewald, T. ; Calzada-Wack, J. ; Ibragimov, E. ; Valenta, M. ; Lukauskas, S. ; Pavesi, A. ; Marschall, S. ; Leuchtenberger, S. ; Fuchs, H. ; Gailus-Durner, V. ; Hrabě de Angelis, M. ; Bultmann, S. ; Rando, O.J. ; Guccione, E. ; Kellner, S.M. ; Schneider, R.

METTL6 is a tRNA m3C methyltransferase that regulates pluripotency and tumor cell growth.

2020 Scientific Article in Nature Communications

Strunz, M.# ; Simon, L.# ; Ansari, M. ; Kathiriya, J.J. ; Angelidis, I. ; Mayr, C. ; Tsidiridis, G. ; Lange, M. ; Mattner, L. ; Yee, M. ; Ogar, P. ; Sengupta, A. ; Kukhtevich, I. ; Schneider, R. ; Zhao, Z. ; Voss, C. ; Stöger, T. ; Neumann, J.H.L. ; Hilgendorff, A. ; Behr, J. ; O'Reilly, M. ; Lehmann, M. ; Burgstaller, G. ; Königshoff, M. ; Chapman, H.A. ; Theis, F.J.&deg ; Schiller, H. B.&deg

Alveolar regeneration through a Krt8+transitional stem cell state that persists in human lung fibrosis.

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Thomas Gerling

Administrative Assistant

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Petra Hammerl

Institute Assistant

Building 90, Room 105