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.
Violetta Peck has joined our lab for working on her medical Phd project. She as well was awarded a GSLS scholarship to characterize receptor-binding-profiles of native gephyrin from mouse-brain-lysates using our microarrays.
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”.
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.
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.
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.
Dr. Hans Maric
Junior Group Leader at the Rudolf Virchow Center of the University of Würzburg (since January 2018)
|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|
|2008 - 2012||Ph.D. Student, Rudolf Virchow Center, Würzburg, Germany|
|2002 - 2008||MSc (Diplom) in Chemistry, University of Würzburg, Germany |
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)
Supervisor – Biomedicine
Member of the Chair for Biophysics and Biotechnology
Biophysics and Molecular Biotechnology
Lecture – Thermodynamics