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English Intern
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin

AG Maric

Über die AG Maric

Proteine sind essentielle Bestandteile aller bekannten Organismen und an praktisch jedem Prozess des Lebens beteiligt. Eine der großen Herausforderungen für die Biowissenschaften im „post-genomischen“ Zeitalter ist es, therapeutisch oder funktionell relevante Proteine zu identifizieren und zu charakterisieren,sowie dieses Wissen auch therapeutisch umzusetzen. Innovationen im Bereich der Automatisierungs- und Miniaturisierungstechnologien ermöglichten kürzlich die Entwicklung von Femto-Molaren-Peptid- und -Protein-Mikroarrays - Eine aufstrebende Schlüsseltechnologie, um auf molekularer Ebene Einblicke in Proteine und ihre Wechselwirkungen zu erhalten.

Microarray-basierte Entwicklung von Protein-Superbindern

Wir produzieren und verwenden solche Microarrays, indem wir die Prinzipien der synthetischen Chemie, Prozesse lebender Organismen und moderne Automatisierungstechnologien kombinieren. Unser Ziel ist es damit neue therapeutische Prinzipien aufzudecken und die Entwicklung neuartiger Biopharmazeutika anzuregen. Zu diesem Zweck verwandeln wir Peptide, Peptid-abgeleitete Verbindungen sowie Nanobody-Varianten in kompakte und hochaffin bindende Moleküle mit optimierten Selektivitätsprofilen - hier "Protein Superbinder" genannt. Aufgrund ihrer vergleichbar geringen Größe und überlegenen Bindungseigenschaften sind solche Moleküle auch als Proteinmarkierungen für hochaufgelöste Mikroskopie geeignet. Mit diesen möchten wir unter anderem helfen das volle Potenzial neuester High-End-Mikroskopie Technologien auszuschöpfen: Eine praktisch molekulare Strukturauflösung sowie quantitative Informationen über die Verteilung der Zielproteine im zellulären Kontext.

Wir sind eine gemeinsame Initiative der Abteilung für Biotechnologie und Biophysik des Biozentrums und des Rudolf-Virchow-Zentrums für Experimentelle Biomedizin. Unsere Arbeitsgruppe wird durch das Programm "Exzellente Ideen" der Universität Würzburg gefördert.

Kurzpräsentation (pdf)

10 October 2019

Rico Petermann has joined our lab for working on his Master Thesis in Biology. The topic of his Master Thesis is “Molecular Basis Syndapin’s Interaction with Inhibitory Posts-Synaptic Proteins”.


11 September 2019

Using an iterative peptide microarray approach Vita Sereikaite successfully developed highly potent peptide-based modulators of GABAB receptor complexes. Her work reveals a fundamentally new approach to affect GABAB receptor function for therapeutic benefit. Publication


12 August 2019

Markus Bayer has joined our lab for working on his medical Phd project. He received the GSLS scholarship to pioneer the direct detection and analysis of autoantibodies in sera of polyneuropathy patients using microarrays.


26 June 2019

Vladimirs`new  article is online. He introduces new strategies to modulate GABAergic signalling. Good job Vladimir! Link to publication


3 June 2019

See you at the ReceptorLight Symposium No.2 in Jena! Clemens, Noah, Vladimir & Hans will present their recent progress in profiling native proteins and developing fluorescent probes.


27 May 2019

Publication in Nature Genetics. The Kubicek lab identified MTHFD1, a folate pathway enzyme, as genetic and physical interactor of the important transcription regulator BRD4. Using our microarray technology we mapped the exact binding interface of the BRD4/MTHFD1 complex.


8 May 2019

Mark Löbel successfully defended his Master Thesis “Inverted Peptides for the Development of Inhibitors of the Ubiquitin-Activating Enzyme”. Thanks Mark for your fantastic contributions to our peptide microarray technology platform and best wishes for your Phd in Oxford, UK!


8 April 2019

Welcome Clemens Schulte! In his Master Thesis he will define and compare protein binding profiles of subpopulations of native proteins within tissue extracts using our microarray technology.


27 March 2019

Publication in Molecular Cell. We supported the Wolf lab in deciphering how oncogenic levels of MYC permit uncontrolled cellular growth. This work revealed new and innovative ways to develop new therapies for cancer.


25 March 2019

Katharina Karch started in our lab as medical Phd candidate. She will use of our microarrays for the diagnosis of multiple sclerosis forms and explore their value to monitor the disease course and therapy success.


25 February 2019

The Maric & Friedmann labs enjoyed a Franconian dinner at “Backöfele”. Thanks for the nice get together everyone!


20 February 2019

Publication in Neuron.  We supported the Schindelin lab in elucidating the molecular basis for Inhibitory Neurotransmission Regulation by Artemisinins. These new findings have the potential to advance the development of medicines for diseases such as Alzheimer's, schizophrenia and epilepsy.


11 February 2019

Graduate student Noah Frieder Nordblom has joined our lab. He was awarded a GSLS scholarship to synthesize novel multivalent fluorescent probes and apply them in microscopy.


7 January 2019

More labspace. You can now find us also in the labs 01.123 and 01.126!


9 August 2018

David Baumstark and Rico Petermann decided to support us to further develop and apply our peptide microarray technology platform!


7 August 2018

Congratulations to Rochelle and Steven for their great work on the collybistin protein that was just accepted in Nature Communications! We identified an exclusive binding of collybistin to the GABAAR-α2-subunit. - Notably, the first report of a high-affinity protein interaction for both proteins. Based on these results Rochelle created knock-in mice and demonstrated that this interaction is critical for the correct targeting and stabilisation of distinct α2-containing GABAAR clusters. She found that interfering with this protein interaction resulted in spontaneous seizures during development, accompanied by early mortality. Surviving mice have increased anxiety-like behavior and EEG abnormalities that are responsive to α2-selective benzodiazepines, revealing a novel therapeutic potential for these compounds. Publication


30 June 2018

Daniel Otzen just published his recent insight into the mechanism of functional Amyloid Formation. Using our microarray-based approach we identified specific motifs that are implicated in amyloid formation. These could lay the foundation for development of peptide-based amyloid inhibitors. Publication


6 June 2018

Neuroscience conference in Schaffhausen, Switzerland. It was a great pleasure to the emerging mechanisms for inhibitory synapse plasticity!  Shuang-Yan & Hans presented their plans how to use the microarray technology to gain molecular level insight into neurobiological processes.


2 May 2018

We welcome biomedicine student Elisa Speth and senior scientist Dr. Shuang-Yan Wang. Dr. Shuang-Yan Wang joined us from Prof. John Robinsons group in Zürich where he developed highly specific cyclic peptidomimetics antibiotics in close cooperation with Polyphor.

 


Sereikaite, V., T. Fritzius, V. Kasaragod, N. Bader, H. M. Maric, H. Schindelin, B. Bettler and K. Strømgaard (2019). Targeting the γ-aminobutyric acid type B (GABAB) receptor complex: Development of inhibitors targeting the K+ channel tetramerization domain (KCTD) containing proteins/GABAB receptor protein-protein interaction. Journal of Medicinal Chemistry. doi: 10.1021/acs.jmedchem.9b01087. [Epub ahead of print]


Khayenko, V., and Maric, H.M. (2019). Targeting GABAAR-Associated Proteins: New Modulators, Labels and Concepts. Frontiers in Molecular Neuroscience 12. doi: 10.3389/fnmol.2019.00162


Sdelci, S., Rendeiro, A.F., Rathert, P., You, W., Lin, J.-M.G., Ringler, A., Hofstätter, G., Moll, H.P., Gürtl, B., Farlik, M., Schick, S., Klepsch, F., Oldach, M., Buphamalai, P., Schischlik, F., Májek, P., Parapatics, K., Schmidl, C., Schuster, M., Penz, T., Buckley, D.L., Hudecz, O., Imre, R., Wang, S.-Y., Maric, H.M., Kralovics, R., Bennett, K.L., Müller, A.C., Mechtler, K., Menche, J., Bradner, J.E., Winter, G.E., Klavins, K., Casanova, E., Bock, C., Zuber, J., and Kubicek, S. (2019). MTHFD1 interaction with BRD4 links folate metabolism to transcriptional regulation. Nature Genetics.  doi: 10.1038/s41588-019-0413-z


Baluapuri A, Hofstetter J, Dudvarski Stankovic N, Endres T, Bhandare P, Vos SM, Adhikari B Schwarz JD, Narain A, Vogt M, Wang SJ, Düster R, Jung LA, Vanselow JT, Wiegering A, Geyer M, Maric HM, Gallant P, Walz S, Schlosser A, Cramer P, Eilers M, Wolf E. MYC recruits SPT5 to RNA polymerase II to promote processive transcription elongation. Molecular Cell (2019) doi.org/10.1016/j.molcel.2019.02.031


Kasaragod, V., Hausrat, T.J., Schaefer, N., Kuhn, M., Christensen, N.R., Tessmer, I., Maric, H.M., Lindegaard Madsen, K., Sotriffer, C., Villmann, C., Kneussel, M., Schindelin, H. Elucidating the Molecular Basis for Inhibitory Neurotransmission Regulation by Artemisinins. Neuron 2019 Jan 28  doi:doi.org/10.1016/j.neuron.2019.01.001


Hines, R., Maric, H.M., Hines, D., Modgil, A., Panzanelli, P., Nakamura, Y., Nathanson, A., Cross, A., Deeb, T., Brandon, N., Davies, P., Fritschy, J.M., Schindelin, H., Moss, S. (2018) Developmental seizures and mortality result from reducing GABAA Receptor α2 subunit interaction with collybistin. Nature Communications, 9, 3130 (2018) doi: 10.1038/s41467-018-05481-1


Bleem, A., Christiansen, G., Madsen, D.J., Maric, H.M., Strømgaard, K., Bryers, J.D., Daggett, V., Meyer, R.L., Otzen, D.E., (2018) Protein Engineering Reveals Mechanisms of Functional Amyloid Formation in Pseudomonas aeruginosa Biofilms, Journal of Molecular Biology (2018) doi.org/10.1016/j.jmb.2018.06.043


Büchel G., Carstensen A., Mak K.Y., Roeschert I., Leen E., Sumara O., Hofstetter J., Herold S., Kalb J., Baluapuri A., Poon W, Kwok C, Chesler L, Maric H.M., Rickman D.S., Wolf E., Bayliss R., Walz S., Eilers M. Association with Aurora-A Controls N-MYC-Dependent Promoter Escape and Pause Release of RNA Polymerase II during the Cell Cycle. Cell Reports, Volume 21 , Issue 12 , 3483 – 3497 (2018) doi  10.1016/j.celrep.2017.11.090


Maric, H. M.*, Hausrat, T. J., Neubert, F., Dalby, N.O., Doose S., Sauer M., Kneussel M., Strømgaard K. (2017), Gephyrin-Binding Peptides Visualize Post-Synaptic Sites and Modulate Neurotransmission, Nature Chemical Biology, 13, 153–160 (2017) doi: 10.1038/nchembio.2246

(*First authorship and shared corresponding authorship)


Cheng J., Sahani S., Hausrat T. J., Yang J. W., Ji H., Schmarowski N., Endle H., Liu X., Li Y., Bottche R., Radyushkin K., Maric H. M., Hoerder-Suabedissen A., Molnar Z., Prouvot P. H., Trimbuch T., Ninnemann O., Huai J., Fan W., Visentin B., Sabbadini R., Strømgaard K., Stroh A., Luhmann H. J., Kneussel M., Nitsch R. Vogt J.  (2016). Precise Somatotopic Thalamocortical Axon Guidance Depends on LPA-Mediated PRG-2/Radixin Signaling. Neuron 92(1): 126-142. doi: 10.1016/j.neuron.2016.08.035


Maric H. M., Kasaragod V. B., Haugaard-Kedström L., Hausrat T. J., Kneussel, M., Schindelin, H. and Strømgaard, K. (2015), Design and Synthesis of High-Affinity Dimeric Inhibitors Targeting the Interactions between Gephyrin and Inhibitory Neurotransmitter Receptors. Angewandte Chemie International Edition 2015, 54, p. 490–494. doi: 10.1002/anie.201409043

Selected as Hot Paper – Outstanding importance in a rapidly evolving field of high current interest


Maric, H. M.*, Kasaragod, V. B.*, Schindelin, H. (2014), Molecular basis of the alternative recruitment of GABAA versus glycine receptors through gephyrin. Nature Communications 2014, 5(5767). doi: 10.1038/ncomms6767

(*shared first authorship)


Maric, H. M., Kasaragod, V. B., Schindelin, H. (2014), Modulation of the Gephyrin-Glycine Receptor Affinity by Multivalency. ACS Chemical Biology 2014, 9(11), p. 2554–2562. doi: 10.1021/cb500303a


Maric, H. M., Mukherjee J., Tretter, V., Moss, S. J., & Schindelin, H. (2011), Gephyrin-mediated γ-Aminobutyric Acid Type A and Glycine Receptor Clustering Relies on a Common Binding Site.The Journal of Biological Chemistry 2011, 286(49), p. 42105-42114. doi:10.1074/jbc.M111.303412


Mukherjee J., Kretschmannova K.*, Gouzer G.*, Maric H. M.*, Ramsden S., Tretter V., Harvey K., Davies P.A., Triller A., Schindelin H., Moss S.J. (2011), The residence time of GABAARs at inhibitory synapses is determined by direct binding of the receptor α1 subunit to gephyrin. The Journal of Neuroscience 2011, 31(41), p. 14677-87. doi:  10.1523/JNEUROSCI.2001-11.2011

(*shared second authorship.)


Tretter V., Kerschner B., Milenkovic I., Ramsden S. L., Ramerstorfer J., Saiepour L., Maric H.M., Moss S. J., Schindelin H., Harvey R. J., Sieghart W., Harvey K. (2011), Molecular basis of the GABAA α3 subunit interaction with the clustering protein gephyrin. The Journal of Biological Chemistry 2011, 286(43): p. 37702-11. doi: 10.1074/jbc.M111.291336.


Tretter V., Mukherjee J., Maric H. M., Schindelin H., Sieghart W., Moss S. J. (2012), Gephyrin, the enigmatic organizer at GABAergic synapses. Frontiers in Cellular Neuroscience 2012. 6: p. 23. doi: 10.3389/fncel.2012.00023.

Sonja Kachler

Technische/r Assistent/in
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Gebäude: Haus D15
Raum: 01.011
Telefon: +49 931 31-80151

Vladimir Khayenko

Doktorand/in
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Gebäude: Haus D15
Raum: 01.012
Telefon: +49 931 31-80218

Dr. Hans Maric

Gruppenleiter
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str.2
97080 Würzburg
Deutschland
Gebäude: Haus D15
Raum: 001.010
Telefon: +49 931 31-85371

Clemens Schulte

Doktorand/in
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2

97080 Würzburg
Deutschland
Gebäude: Haus D15
Raum: 01.012
Telefon: +49 931 31-89734

Current position

Junior Group Leader at the Rudolf Virchow Center of the University of Würzburg (since January 2018)

Research Experience

04/2015-07/2017   Assistant Professor, Center for Biopharmaceuticals, University of Copenhagen, Denmark
07/2013-03/2015 Postdoctoral Fellow, Lundbeck Trust, Copenhagen, Denmark  
12/2012-06/2013 Postdoctoral Fellow, Career Development Fellowship, GSLS Würzburg  
   

Education

2008 - 2012   Ph.D. Student, Rudolf Virchow Center, Würzburg, Germany
2002 - 2008 MSc (Diplom) in Chemistry, University of Würzburg, Germany                                      
 

Patents
Co-inventor of a novel biopharmaceutical substance PA 2015 70783 and PCT DK2016 050369 and co-author of 14 peer-reviewed publications with an accumulated impact of +123, so far yielding over 400 citations.

Fellowships, Awards and External Funding
Association with the CRC/Transregio 166 - Receptor Light (2019)
Material Costs Allowance of the Fonds of the chemical industry (FCI) (2018)
Excellent Ideas Program, Fellowship fo the University of Würzburg (2018 - 2022)
Fonds der chemischen Industrie „Exzellente Ideen“ Programm (2018)
Hoerslev Fonden (2018)
Torben og Alice Frimodts Fond (2017)
Brødrene Hartmanns Fond (2016)
Lundbeck Fellowship (2013 - 2015)
GSLS Career Development Fellowship (2012 - 2013)

Position

Supervisor – Biomedicine
Member of the Chair for Biophysics and Biotechnology

Courses

SS 2018/2019
Biophysics and Molecular Biotechnology