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Rudolf Virchow Center for Experimental Biomedicine

About the Maric Group

Research

Proteins are essential to all known forms of life and participate in virtually every process within cells. Life sciences in the post-genomic era have to face the enormous challenges of identifying and characterising therapeutic and functional relevant proteins. Recent advances in automation and miniaturization facilitated the development of femto molar scale peptide libraries in microchip format - An emerging key technology to gain molecular level insight into proteins and their interactions.

Microarray Based Development of Protein Super Binders

We produce and apply such microarrays by combining the principles of synthetic chemistry, the processes of living organisms and modern automatization technologies with the ultimate goal to uncover novel therapeutic principles and stimulate the development of novel biopharmaceuticals. Using this approach we also aim to complement other driving technologies within Biology and Medical Sciences. To this end, we turn peptides, peptide-derived compounds as well as nanobody variants into compact high affinity binders with optimized selectivity profiles – Herein called “Protein Super Binders”. Due to their comparable small size and superior binding properties, such molecules make ideal protein labels when combined with fluorescent moieties. Thus help to unleash the full potential of high-end microscopy, allowing for virtually molecular structural resolution and quantitative information about the distribution of the target proteins in cellular context.

We are a joint initiative of the Department of Biotechnology and Biophysics of the Biocenter and the Rudolf Virchow Center for Experimental Biomedicine. We are supported by the program “Excellent Ideas” of the University of Würzburg and we are committed to the Cluster of Excellence Inititative: "Enlightening the Receptome: From Biophysics to Clinical Application".

Short Presentation (pdf)

News
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


19 June 2018

Vladimir Khayenko (MSc Pharmacy) started today. He will analyse protein interactions in microchip format and turn the identified binding hot-spots into fluorescent probes for high-end microscopy applications.


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.


18 May 2018

Our research is now supported by the Fonds der Chemischen Industrie (FCI). It is intended as start-up aid for high-performance junior research groups. The funding will be used within the next three years to specifically support the development of our independent research area. The award is given based on outstanding academic achievement and scientific qualification.


15 January 2018

Dr. Shuang-Yan Wang will join our lab as a senior researcher in March 2018. He will map receptor interactions in microchip format and then use the identified binding hot-spots as a starting point for the development of novel nanobodies and antibody mimetics.

Publications

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.

Staff

SonjaKachler

Technische/r Assistent/in
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080Würzburg
Deutschland
Building:Haus D15
Room:01.011

VladimirKhayenko

Doktorand/in
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080Würzburg
Deutschland
Building:Haus D15
Room:01.012

Dr.HansMaric

Gruppenleiter
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str.2
97080Würzburg
Deutschland
Building:Haus D15
Room:001.010

Dr.Shuang-YanWang

Postdoc
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str.2
97080Würzburg
Deutschland
Building:Haus D15
Room:01.012
Curriculum Vitae

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  
12/2012-06/2013Postdoctoral Fellow, Career Development Fellowship, GSLS Würzburg  

Education

2008 - 2012   Ph.D. Student, Rudolf Virchow Center, Würzburg, Germany
2002 - 2008MSc (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 12 peer-reviewed publications with an accumulated impact of +95, so far yielding 329 citations.

Fellowships and Awards
Excellent Ideas Program(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)

Other
Review Editor for Frontiers in Molecular Neuroscience
Scientific advisory boards: Reviewer for the Vienna Science and Technology Fund
Commissioner for chemical safety in the Rudolf Virchow Center
Winner of the 24th Bavarian Team Kendo Championship 2018

Teaching

Position

Supervisor – Biomedicine
Member of the Chair for Biophysics and Biotechnology

Courses

SS 2018/2019
Biophysics and Molecular Biotechnology
Lecture – Thermodynamics

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Contact

Universität Würzburg
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97070 Würzburg

Phone: +49 931 31-0
Fax: +49 931 31-82600

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