Groupleader: Michael Brunner
Michael Brunner
Circadian Rhythms and Molecular Clocks
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Research
Current Research
The Molecular Clock of Neurospora crassa
Most organisms have evolved circadian clocks to anticipate environmental changes associated with the 24h night-day cycle of earth rotation. Circadian clocks modulate rhythmic expression of a large number of genes and thus generate the potential to control biochemical, physiological and behavioral functions in a time-of-day specific manner. Circadian clocks are cell-autonomous oscillators. Eukaryotic circadian clocks are composed of a network of interconnected positive and negative feedback loops that produce rhythmic expression and modification of one or more clock proteins. Circadian oscillations are self-sustained and persist without environmental cues with a ca. 24 h period. In nature, environmental signals, so-called zeitgebers, are transduced to the circadian clock to synchronize the clock with the 24 h period of earth rotation. The strongest zeitgebers are light, temperature and nutrients.
Using the filamentous fungus Neurospora crassa as a model organism, we aim to understand how the circadian clock works as a program that coordinates complex expression profiles in a temporal fashion.
The frequency (frq) gene is a key element of the circadian clock of Neurospora. Expression levels of frq RNA and FRQ protein oscillate in a circadian fashion. Expression of frq is controlled by the heterodimeric transcription factor White Collar Complex (WCC), which activates clock-controlled frq transcription. FRQ assembles with casein kinase 1a (CK1a) and FRQ-Interacting-Helicase (FRH) forming the FFC complex. FFC is a scaffold that interacts transiently with WCC. It inactivates the transcription factor via phosphorylation by CK1a and thereby inhibits synthesis of frq RNA and FRQ protein in a negative feedback. In the course of a day FRQ is progressively hyperphosphorylated. Hyperphosphorylated FRQ releases CK1a. It is then functionally inactive and degraded, resulting in relieve of the negative feedback.
Coordination of the human circadian clock and the cell cycle
The circadian clock and the cell cycle are major cellular systems that organize global physiology in temporal fashion. The circadian clock of mammals is constituted by the core transcription factor BMAL1/CLOCK, which rhythmically activates expression of clock genes including CRYs, PERs, REV-ERBs, and RORs. CRYs and PERs are inhibitors of CLOCK/BMAL whereas REV-ERBs are repressors that control in coordination with ROR activators expression of BMAL1 and CLOCK. The D-box-specific transcription factors E4BP, DBP, TEF and, HLF additionally contribute to the regulation of specific clock genes.
Disruption or misalignment of circadian rhythms in humans has been associated with numerous pathological conditions including cancer. MYC is an oncogene, which is severely deregulated in different cancers and, amplification of MYC often correlates with tumor aggression and poor prognosis. MYC is a transcription factor that supports cell growth and proliferation (cell cycle progression) by regulating transcription of up to 15% of the transcriptome.
MYC is a key regulator that coordinates the circadian clock with cell growth. Overexpression of MYC attenuates the clock and conversely promotes cell proliferation while downregulation of MYC strengthens the clock and reduces proliferation. Inhibition of the circadian clock is crucially dependent on the formation of repressive complexes of MYC with MIZ1 and subsequent downregulation of the core clock genes BMAL1 (ARNTL), CLOCK and NPAS2. BMAL1 expression levels correlate inversely with MYC levels in 102 human lymphomas.
Transcription induced inactivation of promoters/transcriptional memory
mRNA transcripts are often present at only a few copies per cell and many genes are transcribed in bursts, with brief periods of high activity interspersed by long periods of inactivity. Burst size, i.e. the number of transcripts per burst, and burst frequency, i.e. the number of transcriptional bursts per time unit, are gene-specific and appear to depend on the promoter architecture.
We use the natural light-inducible gene expression system based on the transcription activator and blue-light photoreceptor White Collar Complex (WCC) of Neurospora crassa. The system allows repetitive stimulation of transcription within a short period of time. Activation of WCC by a single short light pulse (LP) triggers a synchronized wave of transcription at a large number of promoters. We have observed burst sizes between one and more than 50 transcripts per burst followed by periods of inactivity in the range of hours.
Challenging the frequency (frq) promoter with consecutive light pulses revealed that the promoter supports transcription of ~1 mRNA molecule and then becomes refractory towards further activation for about 45 min. This negative transcriptional memory is dependent on slow chromatin remodelling of the core promoter.
The frq promoter is refractory towards restimulation (T1/2 ~45 min)
Activation frq and vvd promoters by a single LP at t=0 min (black arrow, black curve) or restimulation by a 2nd challenging LP after 15, 30, 60, 90, and 120 min (colored arrows and curves).
CV
| 1989 | PhD, University of Heidelberg |
| 1989-1991 |
Postdoc with J.E. Rothman, Princeton University NJ and Sloan-Kettering Institute, NY. |
| 1992-1998 | Postdoc with W. Neupert, Ludwig Maximilians University, Munich |
| 1998-2000 | Interim professor, Ludwig Maximilians University, Munich |
| Since 2000 | Professor, Heidelberg University Biochemistry Center |
| 2010-2013 | Director of the Heidelberg University Biochemistry Center (BZH) |
| 2013-2014 | Dean of Study, Biochemistry |
| Since 2017 | Member of Leopoldina, Nationale Akademie der Wissenschaften |
| 2019-2020 | Director of the Heidelberg University Biochemistry Center (BZH) |
Lab Members
Sin Min Chan
PhD student
PhD student
Lab:Room 523
/ Phone: +49 6221 54-4289
Mail:sin-min.chan@bzh.uni-heidelberg.de
Axel Diernfellner
staff scientist
staff scientist
Lab:Room 523
/ Phone: +49 6221 54-4289
Office:Room 503
/ Phone: +49 6221 54-4778
Mail:axel.diernfellner@bzh.uni-heidelberg.de
Petra Diestelkötter-Bachert
scientific staff
scientific staff
Lab:Room 523
/ Phone: +49 6221 54-4289
Mail:petra.diestelkoetter-bachert@bzh.uni-heidelberg.de
Martina Franke
secretary
secretary
Office:Room 502
/ Phone: +49 6221 54-4768
Mail:martina.franke@bzh.uni-heidelberg.de
Sekr. Söllner 2.OG: 6:45 - 11:00 Uhr
Sekr. Brunner 5. OG: 11:00 - 14:30 Uhr
Sekr. Söllner 2.OG: 14:30 - 15:15 Uhr
Anna Maria Gatz
PhD student
PhD student
Lab:Room 522
/ Phone: +49 6221 54-4245
Mail:anna-maria.gatz@bzh.uni-heidelberg.de
Leonie Geisser
research assistant
research assistant
Lab:Room 521
/ Phone: +49 6221 54-4342
Mail:leonie.geisser@stud.hs-mannheim.de
Daniela Marzoll
postdoc
postdoc
Lab:Room 523 a
/ Phone: +49 6221 54-4289
Mail:daniela.marzoll@bzh.uni-heidelberg.de
Thomas Pils
TA
TA
Lab:Room 522
/ Phone: +49 6221 54-4245
Office:Room 022
/ Phone: +49 6221 54-4327
Mail:thomas.pils@bzh.uni-heidelberg.de
auch unter Tel. 5862 zu erreichen (wird auf Handy umgeleitet)
Bianca Ruppert
TA
TA
Lab:Room 521
/ Phone: +49 6221 54-4342
Mail:bianca.ruppert@bzh.uni-heidelberg.de
Sabine Schultz
TA
TA
Lab:Room 523
/ Phone: +49 6221 54-4289
Mail:sabine.schultz@bzh.uni-heidelberg.de
Carolin Schunke
PhD student
PhD student
Lab:Room 522
/ Phone: +49 6221 54-4245
Mail:carolin.schunke@bzh.uni-heidelberg.de
Fidel Emmanuel Serrano
PhD student
PhD student
Lab:Room 521
/ Phone: +49 6221 54-4342
Mail:fidel.serrano@bzh.uni-heidelberg.de
Amit Singh
postdoc
postdoc
Office:Room 504
/ Phone: +49 6221 54-4774
Mail:amit.singh@bzh.uni-heidelberg.de
Publications
2021
Singh, A., Schermann, G., Reislöhner, S., Kellner, N., Hurt, E., and Brunner, M. (2021). Global Transcriptome Characterization and Assembly of the Thermophilic Ascomycete Chaetomium thermophilum. Genes 12, 1549. https://doi.org/10.3390/genes12101549
2020
Upadhyay, A., Marzoll, D., Diernfellner, A., Brunner, M. and Herzel, H. (2020). Multiple random phosphorylations in clock proteins provide long delays and switches. Sci Rep 10, 22224
Diernfellner, A. C. R., and Brunner, M. (2020) Phosphorylation Timers in the Neurospora crassa Circadian Clock. J Mol Biol 432, 3449-3465
2019
Shostak, A., Schermann, G., Diernfellner, A., & Brunner, M. (2019). MXD/MIZ1 complexes activate transcription of MYC-repressed genes. BioRxiv, 842799
Upadhyay, A., Brunner, M., and Herzel, H. (2019) An Inactivation Switch Enables Rhythms in a Neurospora Clock Model. Int J Mol Sci 20
Singh, A., Schermann, G., Reislöhner, S., Kellner,N., Hurt, E., Brunner, M. (2019) Global Transcriptome Characterization and Assembly of Thermophilic Ascomycete Chaetomium thermophilum. doi: https://doi.org/10.1101/826354
Shostak, A., and Brunner, M. (2019) Help from my friends-cooperation of BMAL1 with noncircadian transcription factors. Genes Dev 33, 255-257
Diernfellner, A. C. R., Lauinger, L., Shostak, A., and Brunner, M. (2019) A pathway linking translation stress to checkpoint kinase 2 signaling in Neurospora crassa. Proc Natl Acad Sci U S A 116, 17271-17279
2018
Ananthasubramaniam, B., Diernfellner, A., Brunner, M., and Herzel, H. (2018) Ultradian Rhythms in the Transcriptome of Neurospora crassa. iScience 9, 475-486
Lehmann, R., Herzel, H., Brunner, M., Sancar, G., Sancar, C., Ananthasubramaniam, B. (2018) Morning and Evening Peaking Rhythmic Genes are Regulated by Distinct Transcription Factors in Neurospora crassa. Martin Bossert (ed.), Information- and communication Theory in Molecular Biology. Springer: 199-210
2017
Shostak, A., Ruppert, B., Diernfellner, A., and Brunner, M. (2017) Correspondence: Reply to 'Oncogenic MYC persistently upregulates the molecular clock component REV-ERBalpha'. Nat Commun 8, 14918
Lauinger, L., Li, J., Shostak, A., Cemel, I. A., Ha, N., Zhang, Y., Merkl, P. E., Obermeyer, S., Stankovic-Valentin, N., Schafmeier, T., Wever, W. J., Bowers, A. A., Carter, K. P., Palmer, A. E., Tschochner, H., Melchior, F., Deshaies, R. J., Brunner, M., and Diernfellner, A. (2017) Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases. Nat Chem Biol 13, 709-714
Cemel, I. A., Ha, N., Schermann, G., Yonekawa, S., and Brunner, M. (2017) The coding and noncoding transcriptome of Neurospora crassa. BMC Genomics 18, 978
2016
Shostak, A., Ruppert, B., Ha, N., Bruns, P., Toprak, U. H., Project, I. M.-S., Eils, R., Schlesner, M., Diernfellner, A., and Brunner, M. (2016) MYC/MIZ1-dependent gene repression inversely coordinates the circadian clock with cell cycle and proliferation. Nat Commun 7, 11807
Shostak, A., Diernfellner, A., and Brunner, M. (2016) MYC inhibits the clock and supports proliferation. Cell Cycle 15, 3323-3324
2015
Zhai, Z., Kondo, S., Ha, N., Boquete, J. P., Brunner, M., Ueda, R., and Lemaitre, B. (2015) Accumulation of differentiating intestinal stem cell progenies drives tumorigenesis. Nat Commun 6, 10219
Sancar, C., Sancar, G., Ha, N., Cesbron, F., and Brunner, M. (2015) Dawn- and dusk-phased circadian transcription rhythms coordinate anabolic and catabolic functions in Neurospora. BMC Biol 13, 17
Sancar, C., Ha, N., Yilmaz, R., Tesorero, R., Fisher, T., Brunner, M., and Sancar, G. (2015) Combinatorial control of light induced chromatin remodeling and gene activation in Neurospora. PLoS Genet 11, e1005105
Cesbron, F., Oehler, M., Ha, N., Sancar, G., and Brunner, M. (2015) Transcriptional refractoriness is dependent on core promoter architecture. Nat Commun 6, 6753
2014
Sancar, G., and Brunner, M. (2014) Circadian clocks and energy metabolism. Cell Mol Life Sci 71, 2667-2680
Ruger-Herreros, C., Gil-Sanchez Mdel, M., Sancar, G., Brunner, M., and Corrochano, L. M. (2014) Alteration of light-dependent gene regulation by the absence of the RCO-1/RCM-1 repressor complex in the fungus Neurospora crassa. PLoS One 9, e95069
Lee, C. T., Malzahn, E., Brunner, M., and Mayer, M. P. (2014) Light-induced differences in conformational dynamics of the circadian clock regulator VIVID. J Mol Biol 426, 601-610
Lauinger, L., Diernfellner, A., Falk, S., and Brunner, M. (2014) The RNA helicase FRH is an ATP-dependent regulator of CK1a in the circadian clock of Neurospora crassa. Nat Commun 5, 3598
Hoffmann, J., Symul, L., Shostak, A., Fischer, T., Naef, F., and Brunner, M. (2014) Non-circadian expression masking clock-driven weak transcription rhythms in U2OS cells. PLoS One 9, e102238
2013
Gin, E., Diernfellner, A. C., Brunner, M., and Hofer, T. (2013) The Neurospora photoreceptor VIVID exerts negative and positive control on light sensing to achieve adaptation. Mol Syst Biol 9, 667
Cesbron, F., Brunner, M., and Diernfellner, A. C. (2013) Light-dependent and circadian transcription dynamics in vivo recorded with a destabilized luciferase reporter in Neurospora. PLoS One 8, e83660
2012
Tataroglu, O., Lauinger, L., Sancar, G., Jakob, K., Brunner, M., and Diernfellner, A. C. (2012) Glycogen synthase kinase is a regulator of the circadian clock of Neurospora crassa. J Biol Chem 287, 36936-36943
Sancar, G., Sancar, C., and Brunner, M. (2012) Metabolic compensation of the Neurospora clock by a glucose-dependent feedback of the circadian repressor CSP1 on the core oscillator. Genes Dev 26, 2435-2442
Diernfellner, A. C., and Brunner, M. (2012) O-GlcNAcylation of a circadian clock protein: dPER taking its sweet time. Genes Dev 26, 415-416
2011
Schafmeier, T., and Diernfellner, A. C. (2011) Light input and processing in the circadian clock of Neurospora. FEBS Lett 585, 1467-1473
Sancar, G., Sancar, C., Brugger, B., Ha, N., Sachsenheimer, T., Gin, E., Wdowik, S., Lohmann, I., Wieland, F., Hofer, T., Diernfellner, A., and Brunner, M. (2011) A global circadian repressor controls antiphasic expression of metabolic genes in Neurospora. Mol Cell 44, 687-697
Rey, G., Cesbron, F., Rougemont, J., Reinke, H., Brunner, M., and Naef, F. (2011) Genome-wide and phase-specific DNA-binding rhythms of BMAL1 control circadian output functions in mouse liver. PLoS Biol 9, e1000595
Querfurth, C., Diernfellner, A. C., Gin, E., Malzahn, E., Hofer, T., and Brunner, M. (2011) Circadian conformational change of the Neurospora clock protein FREQUENCY triggered by clustered hyperphosphorylation of a basic domain. Mol Cell 43, 713-722
Merrow, M., and Brunner, M. (2011) Circadian rhythms. FEBS Lett 585, 1383
Diernfellner, A. C., and Schafmeier, T. (2011) Phosphorylations: Making the Neurosporacrassa circadian clock tick. FEBS Lett 585, 1461-1466
2010
Tataroglu, O., and Schafmeier, T. (2010) Of switches and hourglasses: regulation of subcellular traffic in circadian clocks by phosphorylation. EMBO Rep 11, 927-935
Smith, K. M., Sancar, G., Dekhang, R., Sullivan, C. M., Li, S., Tag, A. G., Sancar, C., Bredeweg, E. L., Priest, H. D., McCormick, R. F., Thomas, T. L., Carrington, J. C., Stajich, J. E., Bell-Pedersen, D., Brunner, M., and Freitag, M. (2010) Transcription factors in light and circadian clock signaling networks revealed by genomewide mapping of direct targets for neurospora white collar complex. Eukaryot Cell 9, 1549-1556
Malzahn, E., Ciprianidis, S., Kaldi, K., Schafmeier, T., and Brunner, M. (2010) Photoadaptation in Neurospora by competitive interaction of activating and inhibitory LOV domains. Cell 142, 762-772
2009
Sancar, G., Sancar, C., Brunner, M., and Schafmeier, T. (2009) Activity of the circadian transcription factor White Collar Complex is modulated by phosphorylation of SP-motifs. FEBS Lett 583, 1833-1840
Diernfellner, A. C., Querfurth, C., Salazar, C., Hofer, T., and Brunner, M. (2009) Phosphorylation modulates rapid nucleocytoplasmic shuttling and cytoplasmic accumulation of Neurospora clock protein FRQ on a circadian time scale. Genes Dev 23, 2192-2200
2008
Schafmeier, T., Diernfellner, A., Schafer, A., Dintsis, O., Neiss, A., and Brunner, M. (2008) Circadian activity and abundance rhythms of the Neurospora clock transcription factor WCC associated with rapid nucleo-cytoplasmic shuttling. Genes Dev 22, 3397-3402
Neiss, A., Schafmeier, T., and Brunner, M. (2008) Transcriptional regulation and function of the Neurospora clock gene white collar 2 and its isoforms. EMBO Rep 9, 788-794
Brunner, M., Simons, M. J., and Merrow, M. (2008) Lego clocks: building a clock from parts. Genes Dev 22, 1422-1426
Brunner, M., and Merrow, M. (2008) The green yeast uses its plant-like clock to regulate its animal-like tail. Genes Dev 22, 825-831
Brunner, M., and Kaldi, K. (2008) Interlocked feedback loops of the circadian clock of Neurospora crassa. Mol Microbiol 68, 255-262
2007
Querfurth, C., Diernfellner, A., Heise, F., Lauinger, L., Neiss, A., Tataroglu, O., Brunner, M., and Schafmeier, T. (2007) Posttranslational regulation of Neurospora circadian clock by CK1a-dependent phosphorylation. Cold Spring Harb Symp Quant Biol 72, 177-183
Diernfellner, A., Colot, H. V., Dintsis, O., Loros, J. J., Dunlap, J. C., and Brunner, M. (2007) Long and short isoforms of Neurospora clock protein FRQ support temperature-compensated circadian rhythms. FEBS Lett 581, 5759-5764
2006
Schafmeier, T., Kaldi, K., Diernfellner, A., Mohr, C., and Brunner, M. (2006) Phosphorylation-dependent maturation of Neurospora circadian clock protein from a nuclear repressor toward a cytoplasmic activator. Genes Dev 20, 297-306
Kaldi, K., Gonzalez, B. H., and Brunner, M. (2006) Transcriptional regulation of the Neurospora circadian clock gene wc-1 affects the phase of circadian output. EMBO Rep 7, 199-204
Brunner, M., and Diernfellner, A. (2006) How temperature affects the circadian clock of Neurospora crassa. Chronobiol Int 23, 81-90
2005
Schafmeier, T., Haase, A., Kaldi, K., Scholz, J., Fuchs, M., and Brunner, M. (2005) Transcriptional feedback of Neurospora circadian clock gene by phosphorylation-dependent inactivation of its transcription factor. Cell 122, 235-246
Diernfellner, A. C., Schafmeier, T., Merrow, M. W., and Brunner, M. (2005) Molecular mechanism of temperature sensing by the circadian clock of Neurospora crassa. Genes Dev 19, 1968-1973
2002
Okamoto, K., Brinker, A., Paschen, S. A., Moarefi, I., Hayer-Hartl, M., Neupert, W., and Brunner, M. (2002) The protein import motor of mitochondria: a targeted molecular ratchet driving unfolding and translocation. EMBO J 21, 3659-3671
Moro, F., Okamoto, K., Donzeau, M., Neupert, W., and Brunner, M. (2002) Mitochondrial protein import: molecular basis of the ATP-dependent interaction of MtHsp70 with Tim44. J Biol Chem 277, 6874-6880
2001
Rothbauer, U., Hofmann, S., Muhlenbein, N., Paschen, S. A., Gerbitz, K. D., Neupert, W., Brunner, M., and Bauer, M. F. (2001) Role of the deafness dystonia peptide 1 (DDP1) in import of human Tim23 into the inner membrane of mitochondria. J Biol Chem 276, 37327-37334
Milisav, I., Moro, F., Neupert, W., and Brunner, M. (2001) Modular structure of the TIM23 preprotein translocase of mitochondria. J Biol Chem 276, 25856-25861
Merrow, M., Franchi, L., Dragovic, Z., Gorl, M., Johnson, J., Brunner, M., Macino, G., and Roenneberg, T. (2001) Circadian regulation of the light input pathway in Neurospora crassa. EMBO J 20, 307-315
Gorl, M., Merrow, M., Huttner, B., Johnson, J., Roenneberg, T., and Brunner, M. (2001) A PEST-like element in FREQUENCY determines the length of the circadian period in Neurospora crassa. EMBO J 20, 7074-7084
2000
Paschen, S. A., Rothbauer, U., Kaldi, K., Bauer, M. F., Neupert, W., and Brunner, M. (2000) The role of the TIM8-13 complex in the import of Tim23 into mitochondria. EMBO J 19, 6392-6400
Donzeau, M., Kaldi, K., Adam, A., Paschen, S., Wanner, G., Guiard, B., Bauer, M. F., Neupert, W., and Brunner, M. (2000) Tim23 links the inner and outer mitochondrial membranes. Cell 101, 401-412
Cruciat, C. M., Brunner, S., Baumann, F., Neupert, W., and Stuart, R. A. (2000) The cytochrome bc1 and cytochrome c oxidase complexes associate to form a single supracomplex in yeast mitochondria. J Biol Chem 275, 18093-18098
Bauer, M. F., Hofmann, S., Neupert, W., and Brunner, M. (2000) Protein translocation into mitochondria: the role of TIM complexes. Trends Cell Biol 10, 25-31
Bauer, M.F., Paschen, S.A., Neupert, W. and Brunner, M. (2000) Mechanisms of mitochondrial protein import. Protoplasma 213, 1-10.
1999
Moro, F., Sirrenberg, C., Schneider, H. C., Neupert, W., and Brunner, M. (1999) The TIM17.23 preprotein translocase of mitochondria: composition and function in protein transport into the matrix. EMBO J 18, 3667-3675
Merrow, M., Brunner, M., and Roenneberg, T. (1999) Assignment of circadian function for the Neurospora clock gene frequency. Nature 399, 584-586
Endres, M., Neupert, W., and Brunner, M. (1999) Transport of the ADP/ATP carrier of mitochondria from the TOM complex to the TIM22.54 complex. EMBO J 18, 3214-3221
Bauer, M. F., Rothbauer, U., Muhlenbein, N., Smith, R. J., Gerbitz, K., Neupert, W., Brunner, M., and Hofmann, S. (1999) The mitochondrial TIM22 preprotein translocase is highly conserved throughout the eukaryotic kingdom. FEBS Lett 464, 41-47
Bauer, M. F., Gempel, K., Reichert, A. S., Rappold, G. A., Lichtner, P., Gerbitz, K. D., Neupert, W., Brunner, M., and Hofmann, S. (1999) Genetic and structural characterization of the human mitochondrial inner membrane translocase. J Mol Biol 289, 69-82
Adam, A., Endres, M., Sirrenberg, C., Lottspeich, F., Neupert, W., and Brunner, M. (1999) Tim9, a new component of the TIM22.54 translocase in mitochondria. EMBO J 18, 313-319
1998
Sirrenberg, C., Endres, M., Folsch, H., Stuart, R. A., Neupert, W., and Brunner, M. (1998) Carrier protein import into mitochondria mediated by the intermembrane proteins Tim10/Mrs11 and Tim12/Mrs5. Nature 391, 912-915
Rapaport, D., Brunner, M., Neupert, W., and Westermann, B. (1998) Fzo1p is a mitochondrial outer membrane protein essential for the biogenesis of functional mitochondria in Saccharomyces cerevisiae. J Biol Chem 273, 20150-20155
Kaldi, K., Bauer, M. F., Sirrenberg, C., Neupert, W., and Brunner, M. (1998) Biogenesis of Tim23 and Tim17, integral components of the TIM machinery for matrix-targeted preproteins. EMBO J 17, 1569-1576
Gaume, B., Klaus, C., Ungermann, C., Guiard, B., Neupert, W., and Brunner, M. (1998) Unfolding of preproteins upon import into mitochondria. EMBO J 17, 6497-6507
Folsch, H., Gaume, B., Brunner, M., Neupert, W., and Stuart, R. A. (1998) C- to N-terminal translocation of preproteins into mitochondria. EMBO J 17, 6508-6515
Bauer, M. F., Künkele, K. P., Neupert, W. and Brunner, M. (1998) Proteine auf Reisen. Einsichten 2, 14-17.
1997
Sirrenberg, C., Endres, M., Becker, K., Bauer, M. F., Walther, E., Neupert, W., and Brunner, M. (1997) Functional cooperation and stoichiometry of protein translocases of the outer and inner membranes of mitochondria. J Biol Chem 272, 29963-29966
Arnold, I., Bauer, M. F., Brunner, M., Neupert, W., and Stuart, R. A. (1997) Yeast mitochondrial F1F0-ATPase: the novel subunit e is identical to Tim11. FEBS Lett 411, 195-200
1996
Sirrenberg, C., Bauer, M. F., Guiard, B., Neupert, W., and Brunner, M. (1996) Import of carrier proteins into the mitochondrial inner membrane mediated by Tim22. Nature 384, 582-585
Schneider, H. C., Westermann, B., Neupert, W., and Brunner, M. (1996) The nucleotide exchange factor MGE exerts a key function in the ATP-dependent cycle of mt-Hsp70-Tim44 interaction driving mitochondrial protein import. EMBO J 15, 5796-5803
Klaus, C., Guiard, B., Neupert, W., and Brunner, M. (1996) Determinants in the presequence of cytochrome b2 for import into mitochondria and for proteolytic processing. Eur J Biochem 236, 856-861
Bauer, M. F., Sirrenberg, C., Neupert, W., and Brunner, M. (1996) Role of Tim23 as voltage sensor and presequence receptor in protein import into mitochondria. Cell 87, 33-41
Schneider, H. C., Berthold, J., Bauer, M. F., Klaus, C., Neupert, W. and Brunner, M. (1996) Protein import across the inner mitochondrial membrane. NATO ASI Series H96, 157-165.
1995
Brunner, M., Schneider, H. C., Lill, R., and Neupert, W. (1995) Dissection of protein translocation across the mitochondrial outer and inner membranes. Cold Spring Harb Symp Quant Biol 60, 619-627
Brunner, M., and Neupert, W. (1995) Purification and characterization of mitochondrial processing peptidase of Neurospora crassa. Methods Enzymol 248, 717-728
Berthold, J., Bauer, M. F., Schneider, H. C., Klaus, C., Dietmeier, K., Neupert, W., and Brunner, M. (1995) The MIM complex mediates preprotein translocation across the mitochondrial inner membrane and couples it to the mt-Hsp70/ATP driving system. Cell 81, 1085-1093
1994
Whiteheart, S. W., Rossnagel, K., Buhrow, S. A., Brunner, M., Jaenicke, R., and Rothman, J. E. (1994) N-ethylmaleimide-sensitive fusion protein: a trimeric ATPase whose hydrolysis of ATP is required for membrane fusion. J Cell Biol 126, 945-954
Schneider, H. C., Berthold, J., Bauer, M. F., Dietmeier, K., Guiard, B., Brunner, M., and Neupert, W. (1994) Mitochondrial Hsp70/MIM44 complex facilitates protein import. Nature 371, 768-774
Bassham, D. C., Creighton, A. M., Arretz, M., Brunner, M., and Robinson, C. (1994) Efficient but aberrant cleavage of mitochondrial precursor proteins by the chloroplast stromal processing peptidase. Eur J Biochem 221, 523-528
Arretz, M., Schneider, H., Guiard, B., Brunner, M., and Neupert, W. (1994) Characterization of the mitochondrial processing peptidase of Neurospora crassa. J Biol Chem 269, 4959-4967
Brunner, M., Klaus, C. and Neupert, W. (1994) The mitochondrial processing peptidase. In Heijne, G (ed.) Signal Peptidases, RG Landes Comp, 73-86.
Brunner, M. and Whiteheart, S. W. (1994) Mammalian Proteins involved in membrane traffic in the Golgi and to the cell surface - SNAP. In Rothblatt, J, Novick, P and Stevens, T (eds.) Guidebook to the secretory pathway, Sambrook and Tooze publication at Oxford University press, 180-181.
1993
Whiteheart, S. W., Griff, I. C., Brunner, M., Clary, D. O., Mayer, T., Buhrow, S. A., and Rothman, J. E. (1993) SNAP family of NSF attachment proteins includes a brain-specific isoform. Nature 362, 353-355
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Resources
Neurospora Crassa
Neurospora crassa is an ascomycete red bread mold. Like all fungi, it reproduces by spores. Neurospora became a model organism, diverse range of research programme conducted on Neurospora such as molecular genetics, biochemistry, physiology, molecular cell biology photobiology, circadian rhythms, gene silencing, ecology, and evolution. Our group mostly focuses research on circadian rhythms using Chip seq, RNAseq in different experimental conditions. NEUTRA (Neurospora crassa Transcriptome Database) was created to visualize the normalized RNA-seq and ChIP-seq datasets of the selected genes with Google Charts as well as genome browser with the following link.
https://neutra.bzh.uni-heidelberg.de
Citation: The coding and noncoding transcriptome of Neurospora crassa
Ibrahim Avi Cemel , Nati Ha, Geza Schermann, Shusuke Yonekawa and Michael Brunner
DOI 10.1186/s12864-017-4360-8
Contacts:
ibrahim.cemel@bzh.uni-heidelberg.de
geza.schermann@bzh.uni-heidelberg.de
https://neutra.bzh.uni-heidelberg.de
Citation: The coding and noncoding transcriptome of Neurospora crassa
Ibrahim Avi Cemel , Nati Ha, Geza Schermann, Shusuke Yonekawa and Michael Brunner
DOI 10.1186/s12864-017-4360-8
Contacts:
ibrahim.cemel@bzh.uni-heidelberg.de
geza.schermann@bzh.uni-heidelberg.de
Chaetomium thermophilum
The Chaetomium is a thermophilic filamentous fungus, having the ability to grow at 50 − 55◦ C. It produces different thermostable enzymes such as cellulase, xylanase, laccase, chitinases, and proteases. Due to the thermostability nature of C.thermophilum, various industries used this organism for starch degradation, hydrolysis of cellulose for bioethanol production as well as other applications requiring enzymatic activities at higher temperatures. The genomic and transcriptomic sequence data often interpreted by functional annotation through Gene Ontology (GO) database. Here, we created an R Package for gene as well as GO annotation which can be found in below links. Additionally, we created a lookup file which contains genomic features, gene id corresponding to GO term and Enzyme Commission number (EC) which can be useful in an industrial application as well as basic research on C.thermophilum.
Gene and GO annotation Package
TxDb.Chaetomium.ct39.knownGene_1.0.0.tar.gz
org.Cthermophilum.eg.db_1.0.0.tar.gz
Package Installation in R
R CMD install TxDb.Chaetomium.ct39.knownGene_1.0.0.tar.gz
R CMD install org.Cthermophilum.eg.db_1.0.0.tar.gz
Further information, contact:
michael.brunner@bzh.uni-heidelberg.de
geza.schermann@bzh.uni-heidelberg.de
amit.singh@bzh.uni-heidelberg.de
Contact
Sprechstunde: donnerstags, 10.30 - 11.30 Uhr Heidelberg University
Biochemistry Center (BZH)
Im Neuenheimer Feld 328
69120 Heidelberg
Biochemistry Center (BZH)
Im Neuenheimer Feld 328
69120 Heidelberg
Office:
+49 6221 54-4207 Fax:
+49 6221 54-4769 E-Mail:
michael.brunner@bzh.uni-heidelberg.deSecretary: Martina Franke
Office:
+49 6221 54-4768 Fax:
+49 6221 54-4769 E-Mail:
martina.franke@bzh.uni-heidelberg.de