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Groupleader: Michael Brunner

Circadian Rhythms and Molecular Clocks 

Group Leader 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).

 

Download BZH Report Brunner 2014-2016

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

Lab:Room 523 / Phone: +49 6221 54-4289
Mail:sin-min.chan@bzh.uni-heidelberg.de

 RoomPhone
LAB 523 +49 6221 54-4289
E-Mail sin-min.chan@bzh.uni-heidelberg.de
Axel Diernfellner
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

 RoomPhone
LAB 523 +49 6221 54-4289
OFFICE 503 +49 6221 54-4778
E-Mail axel.diernfellner@bzh.uni-heidelberg.de
Petra Diestelkötter-Bachert
scientific staff

Lab:Room 523 / Phone: +49 6221 54-4289
Mail:petra.diestelkoetter-bachert@bzh.uni-heidelberg.de

 RoomPhone
LAB 523 +49 6221 54-4289
E-Mail petra.diestelkoetter-bachert@bzh.uni-heidelberg.de
Martina Franke
secretary

Office:Room 502 / Phone: +49 6221 54-4768
Mail:martina.franke@bzh.uni-heidelberg.de

Sekr. Söllner 2.OG: 6:45 - 10:00 Uhr
Sekr. Brunner 5. OG: 10:00 - 14:00 Uhr
Sekr. Söllner 2.OG: 14:00 - 15:15 Uhr

 RoomPhone
OFFICE 502 +49 6221 54-4768
E-Mail martina.franke@bzh.uni-heidelberg.de
Anna Maria Gatz
postdoc

Lab:Room 522 / Phone: +49 6221 54-4245
Mail:anna-maria.gatz@bzh.uni-heidelberg.de

 RoomPhone
LAB 522 +49 6221 54-4245
E-Mail anna-maria.gatz@bzh.uni-heidelberg.de
Daniela Marzoll
postdoc

Lab:Room 523 a / Phone: +49 6221 54-4289
Mail:daniela.marzoll@bzh.uni-heidelberg.de

 RoomPhone
LAB 523 a +49 6221 54-4289
E-Mail daniela.marzoll@bzh.uni-heidelberg.de
Thomas Pils
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)

 RoomPhone
LAB 522 +49 6221 54-4245
OFFICE 022 +49 6221 54-4327
E-Mail thomas.pils@bzh.uni-heidelberg.de
Bianca Ruppert
TA

Lab:Room 521 / Phone: +49 6221 54-4342
Mail:bianca.ruppert@bzh.uni-heidelberg.de

 RoomPhone
LAB 521 +49 6221 54-4342
E-Mail bianca.ruppert@bzh.uni-heidelberg.de
Sabine Schultz
TA

Lab:Room 523 / Phone: +49 6221 54-4289
Mail:sabine.schultz@bzh.uni-heidelberg.de

 RoomPhone
LAB 523 +49 6221 54-4289
E-Mail sabine.schultz@bzh.uni-heidelberg.de
Carolin Schunke
PhD student

Lab:Room 522 / Phone: +49 6221 54-4245
Mail:carolin.schunke@bzh.uni-heidelberg.de

 RoomPhone
LAB 522 +49 6221 54-4245
E-Mail carolin.schunke@bzh.uni-heidelberg.de
Fidel Emmanuel Serrano
PhD student

Lab:Room 521 / Phone: +49 6221 54-4342
Mail:fidel.serrano@bzh.uni-heidelberg.de

 RoomPhone
LAB 521 +49 6221 54-4342
E-Mail fidel.serrano@bzh.uni-heidelberg.de

Publications 


Adaptation to glucose starvation is associated with molecular reorganization of the circadian clock in Neurospora crassa. Elife. 2023; PMC9831608. doi:10.7554/eLife.79765. Szőke, A., Sárkány, O., Schermann, G., Kapuy, O., Diernfellner, A. C. R., Brunner, M., Gyöngyösi, N. and Káldi, K. (2023)

Antisense Transcription of the Neurospora Frequency Gene Is Rhythmically Regulated by CSP-1 Repressor but Dispensable for Clock Function. J Biol Rhythms. 2023; doi:10.1177/07487304231153914. Cemel, I. A., Diernfellner, A. C. R. and Brunner, M. (2023)

Casein kinase 1 and disordered clock proteins form functionally equivalent, phospho-based circadian modules in fungi and mammals. Proc Natl Acad Sci U S A. 2022; PMC8892514. doi:10.1073/pnas.2118286119. Marzoll, D., Serrano, F. E., Shostak, A., Schunke, C., Diernfellner, A. C. R. and Brunner, M. (2022)

Data-driven modelling captures dynamics of the circadian clock of Neurospora crassa. PLoS Comput Biol. 2022; PMC9397904. doi:10.1371/journal.pcbi.1010331. Singh, A., Li, C., Diernfellner, A. C. R., Höfer, T. and Brunner, M. (2022)

How circadian clocks keep time: the discovery of slowness. FEBS Lett. 2022; doi:10.1002/1873-3468.14432. Partch, C. and Brunner, M. (2022)

Neurospora casein kinase 1a recruits the circadian clock protein FRQ via the C-terminal lobe of its kinase domain. FEBS Lett. 2022; doi:10.1002/1873-3468.14435. Marzoll, D., Serrano, F. E., Diernfellner, A. C. R. and Brunner, M. (2022)

Global Transcriptome Characterization and Assembly of the Thermophilic Ascomycete Chaetomium thermophilum. Genes (Basel). 2021; PMC8535861. doi:10.3390/genes12101549. Singh, A., Schermann, G., Reislöhner, S., Kellner, N., Hurt, E. and Brunner, M. (2021)

MXD/MIZ1 transcription regulatory complexes activate the expression of MYC-repressed genes. FEBS Lett. 2021; doi:10.1002/1873-3468.14097. Shostak, A., Schermann, G., Diernfellner, A. and Brunner, M. (2021)

Multiple random phosphorylations in clock proteins provide long delays and switches. Sci Rep. 2020; PMC7746754. doi:10.1038/s41598-020-79277-z. Upadhyay, A., Marzoll, D., Diernfellner, A., Brunner, M. and Herzel, H. (2020)

Phosphorylation Timers in the Neurospora crassa Circadian Clock. J Mol Biol. 2020; doi:10.1016/j.jmb.2020.04.004. Diernfellner, A. C. R. and Brunner, M. (2020)

A pathway linking translation stress to checkpoint kinase 2 signaling in Neurospora crassa. Proc Natl Acad Sci U S A. 2019; PMC6717302. doi:10.1073/pnas.1815396116. Diernfellner, A. C. R., Lauinger, L., Shostak, A. and Brunner, M. (2019)

An Inactivation Switch Enables Rhythms in a Neurospora Clock Model. Int J Mol Sci. 2019; PMC6627049. doi:10.3390/ijms20122985. Upadhyay, A., Brunner, M. and Herzel, H. (2019)

Help from my friends-cooperation of BMAL1 with noncircadian transcription factors. Genes Dev. 2019; PMC6411012. doi:10.1101/gad.324046.119. Shostak, A. and Brunner, M. (2019)

Morning and Evening Peaking Rhythmic Genes are Regulated by Distinct Transcription Factors in Neurospora crassa. in Information- and communication Theory in Molecular Biology (ed. M. Bossert), pp. 199-210. Springer. Lehmann, R., Herzel, H., Brunner, M., Sancar, G., Sancar, C. and Ananthasubramaniam, B. (2018)

Frequency Modulation of Transcriptional Bursting Enables Sensitive and Rapid Gene Regulation. Cell Syst. 2018; doi:10.1016/j.cels.2018.01.012. Li, C., Cesbron, F., Oehler, M., Brunner, M. and Höfer, T. (2018)

Ultradian Rhythms in the Transcriptome of Neurospora crassa. iScience 9, 475-486.
Ananthasubramaniam, B., Diernfellner, A., Brunner, M., and Herzel, H. (2018)

Correspondence: Reply to 'Oncogenic MYC persistently upregulates the molecular clock component REV-ERBα'. Nat Commun. 2017; PMC5376643. doi:10.1038/ncomms14918. Shostak, A., Ruppert, B., Diernfellner, A. and Brunner, M. (2017)

The coding and noncoding transcriptome of Neurospora crassa. BMC Genomics. 2017; PMC5738166. doi:10.1186/s12864-017-4360-8. Cemel, I. A., Ha, N., Schermann, G., Yonekawa, S. and Brunner, M. (2017)

Thiolutin is a zinc chelator that inhibits the Rpn11 and other JAMM metalloproteases. Nat Chem Biol. 2017; PMC5792653. doi:10.1038/nchembio.2370. 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)

MYC inhibits the clock and supports proliferation. Cell Cycle. 2016; PMC5224463. doi:10.1080/15384101.2016.1224760. Shostak, A., Diernfellner, A. and Brunner, M. (2016)

MYC/MIZ1-dependent gene repression inversely coordinates the circadian clock with cell cycle and proliferation. Nat Commun. 2016; PMC4931031. doi:10.1038/ncomms11807. Shostak, A., Ruppert, B., Ha, N., Bruns, P., Toprak, U. H., Eils, R., Schlesner, M., Diernfellner, A. and Brunner, M. (2016)

Accumulation of differentiating intestinal stem cell progenies drives tumorigenesis. Nat Commun. 2015; PMC4703904. doi:10.1038/ncomms10219. Zhai, Z., Kondo, S., Ha, N., Boquete, J. P., Brunner, M., Ueda, R. and Lemaitre, B. (2015)

Combinatorial control of light induced chromatin remodeling and gene activation in Neurospora. PLoS Genet. 2015; PMC4378982. doi:10.1371/journal.pgen.1005105. Sancar, C., Ha, N., Yilmaz, R., Tesorero, R., Fisher, T., Brunner, M. and Sancar, G. (2015)

Dawn- and dusk-phased circadian transcription rhythms coordinate anabolic and catabolic functions in Neurospora. BMC Biol 13, 17. Sancar, C., Sancar, G., Ha, N., Cesbron, F. and Brunner, M. (2015)

Transcriptional refractoriness is dependent on core promoter architecture. Nat Commun. 2015; doi:10.1038/ncomms7753. Cesbron, F., Oehler, M., Ha, N., Sancar, G. and Brunner, M. (2015)

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.
Ruger-Herreros, C., Gil-Sanchez Mdel, M., Sancar, G., Brunner, M., and Corrochano, L. M. (2014)

Circadian clocks and energy metabolism. Cell Mol Life Sci. 2014; doi:10.1007/s00018-014-1574-7. Sancar, G. and Brunner, M. (2014)

Light-induced differences in conformational dynamics of the circadian clock regulator VIVID. J Mol Biol. 2014; doi:10.1016/j.jmb.2013.10.035. Lee, C. T., Malzahn, E., Brunner, M. and Mayer, M. P. (2014)

Non-circadian expression masking clock-driven weak transcription rhythms in U2OS cells. PLoS One. 2014; PMC4090172. doi:10.1371/journal.pone.0102238. Hoffmann, J., Symul, L., Shostak, A., Fischer, T., Naef, F. and Brunner, M. (2014)

The RNA helicase FRH is an ATP-dependent regulator of CK1a in the circadian clock of Neurospora crassa. Nat Commun. 2014; doi:10.1038/ncomms4598. Lauinger, L., Diernfellner, A., Falk, S. and Brunner, M. (2014)

Light-dependent and circadian transcription dynamics in vivo recorded with a destabilized luciferase reporter in Neurospora. PLoS One. 2013; PMC3877077. doi:10.1371/journal.pone.0083660. Cesbron, F., Brunner, M. and Diernfellner, A. C. (2013)

The Neurospora photoreceptor VIVID exerts negative and positive control on light sensing to achieve adaptation. Mol Syst Biol. 2013; PMC4039372. doi:10.1038/msb.2013.24. Gin, E., Diernfellner, A. C., Brunner, M. and Höfer, T. (2013)

Glycogen synthase kinase is a regulator of the circadian clock of Neurospora crassa. J Biol Chem. 2012; PMC3481296. doi:10.1074/jbc.M112.396622. Tataroğlu, Ö., Lauinger, L., Sancar, G., Jakob, K., Brunner, M. and Diernfellner, A. C. (2012)

Metabolic compensation of the Neurospora clock by a glucose-dependent feedback of the circadian repressor CSP1 on the core oscillator. Genes Dev. 2012; PMC3490001. doi:10.1101/gad.199547.112. Sancar, G., Sancar, C. and Brunner, M. (2012)

O-GlcNAcylation of a circadian clock protein: dPER taking its sweet time. Genes Dev. 2012; PMC3305979. doi:10.1101/gad.188524.112. Diernfellner, A. C. and Brunner, M. (2012)

A global circadian repressor controls antiphasic expression of metabolic genes in Neurospora. Mol Cell. 2011; doi:10.1016/j.molcel.2011.10.019. Sancar, G., Sancar, C., Brügger, B., Ha, N., Sachsenheimer, T., Gin, E., Wdowik, S., Lohmann, I., Wieland, F., Höfer, T., Diernfellner, A. and Brunner, M. (2011)

Circadian conformational change of the Neurospora clock protein FREQUENCY triggered by clustered hyperphosphorylation of a basic domain. Mol Cell. 2011; doi:10.1016/j.molcel.2011.06.033. Querfurth, C., Diernfellner, A. C., Gin, E., Malzahn, E., Höfer, T. and Brunner, M. (2011)

Circadian rhythms. FEBS Lett. 2011; doi:10.1016/j.febslet.2011.04.055. Merrow, M. and Brunner, M. (2011)

Die Entstehung und Entwicklung des Biochemie-Zentrums. in Wissenschaftsatlas der Universität Heidelberg 1386 – 2011, pp. 222-224. BIBLIOTHECA PALATINA Verlag. Schafmeier, T., Franke-Schaub, M., Schirmer, R. H. and Brunner, M. (2011)

Genome-wide and phase-specific DNA-binding rhythms of BMAL1 control circadian output functions in mouse liver. PLoS Biol. 2011; PMC3043000. doi:10.1371/journal.pbio.1000595. Rey, G., Cesbron, F., Rougemont, J., Reinke, H., Brunner, M. and Naef, F. (2011)

Light input and processing in the circadian clock of Neurospora. FEBS Lett 585, 1467-1473.
Schafmeier, T., and Diernfellner, A. C. (2011)

Phosphorylations: Making the Neurosporacrassa circadian clock tick. FEBS Lett 585, 1461-1466.
Diernfellner, A. C., and Schafmeier, T. (2011)

Of switches and hourglasses: regulation of subcellular traffic in circadian clocks by phosphorylation. EMBO Rep 11, 927-935.
Tataroglu, O., and Schafmeier, T. (2010)

Photoadaptation in Neurospora by competitive interaction of activating and inhibitory LOV domains. Cell. 2010; doi:10.1016/j.cell.2010.08.010. Malzahn, E., Ciprianidis, S., Káldi, K., Schafmeier, T. and Brunner, 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. 2010; PMC2950426. doi:10.1128/ec.00154-10. 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)

Activity of the circadian transcription factor White Collar Complex is modulated by phosphorylation of SP-motifs. FEBS Lett. 2009; doi:10.1016/j.febslet.2009.04.042. Sancar, G., Sancar, C., Brunner, M. and Schafmeier, T. (2009)

Phosphorylation modulates rapid nucleocytoplasmic shuttling and cytoplasmic accumulation of Neurospora clock protein FRQ on a circadian time scale. Genes Dev. 2009; PMC2751991. doi:10.1101/gad.538209. Diernfellner, A. C., Querfurth, C., Salazar, C., Höfer, T. and Brunner, M. (2009)

Interlocked feedback loops of the circadian clock of Neurospora crassa. Mol Microbiol. 2008; doi:10.1111/j.1365-2958.2008.06148.x. Brunner, M. and Káldi, K. (2008)

Circadian activity and abundance rhythms of the Neurospora clock transcription factor WCC associated with rapid nucleo-cytoplasmic shuttling. Genes Dev. 2008; PMC2607078. doi:10.1101/gad.507408. Schafmeier, T., Diernfellner, A., Schäfer, A., Dintsis, O., Neiss, A. and Brunner, M. (2008)

Lego clocks: building a clock from parts. Genes Dev. 2008; PMC2732415. doi:10.1101/gad.1686608. Brunner, M., Simons, M. J. and Merrow, M. (2008)

The green yeast uses its plant-like clock to regulate its animal-like tail. Genes Dev. 2008; PMC2732389. doi:10.1101/gad.1664508. Brunner, M. and Merrow, M. (2008)

Transcriptional regulation and function of the Neurospora clock gene white collar 2 and its isoforms. EMBO Rep. 2008; PMC2515204. doi:10.1038/embor.2008.113. Neiss, A., Schafmeier, T. and Brunner, M. (2008)

Long and short isoforms of Neurospora clock protein FRQ support temperature-compensated circadian rhythms. FEBS Lett. 2007; PMC2704016. doi:10.1016/j.febslet.2007.11.043. Diernfellner, A., Colot, H. V., Dintsis, O., Loros, J. J., Dunlap, J. C. and Brunner, M. (2007)

Posttranslational regulation of Neurospora circadian clock by CK1a-dependent phosphorylation. Cold Spring Harb Symp Quant Biol. 2007; doi:10.1101/sqb.2007.72.025. Querfurth, C., Diernfellner, A., Heise, F., Lauinger, L., Neiss, A., Tataroglu, O., Brunner, M. and Schafmeier, T. (2007)

How temperature affects the circadian clock of Neurospora crassa. Chronobiol Int. 2006; doi:10.1080/07420520500545805. Brunner, M. and Diernfellner, A. (2006)

Phosphorylation-dependent maturation of Neurospora circadian clock protein from a nuclear repressor toward a cytoplasmic activator. Genes Dev. 2006; PMC1361701. doi:10.1101/gad.360906. Schafmeier, T., Káldi, K., Diernfellner, A., Mohr, C. and Brunner, M. (2006)

Transcriptional regulation of the Neurospora circadian clock gene wc-1 affects the phase of circadian output. EMBO Rep. 2006; PMC1369249. doi:10.1038/sj.embor.7400595. Káldi, K., González, B. H. and Brunner, M. (2006)

Molecular mechanism of temperature sensing by the circadian clock of Neurospora crassa. Genes Dev. 2005; PMC1199567. doi:10.1101/gad.345905. Diernfellner, A. C., Schafmeier, T., Merrow, M. W. and Brunner, M. (2005)

Transcriptional feedback of Neurospora circadian clock gene by phosphorylation-dependent inactivation of its transcription factor. Cell. 2005; doi:10.1016/j.cell.2005.05.032. Schafmeier, T., Haase, A., Káldi, K., Scholz, J., Fuchs, M. and Brunner, M. (2005)

Mitochondrial protein import: molecular basis of the ATP-dependent interaction of MtHsp70 with Tim44. J Biol Chem. 2002; doi:10.1074/jbc.M107935200. Moro, F., Okamoto, K., Donzeau, M., Neupert, W. and Brunner, M. (2002)

The protein import motor of mitochondria: a targeted molecular ratchet driving unfolding and translocation. Embo j. 2002; PMC126104. doi:10.1093/emboj/cdf358. Okamoto, K., Brinker, A., Paschen, S. A., Moarefi, I., Hayer-Hartl, M., Neupert, W. and Brunner, M. (2002)

A PEST-like element in FREQUENCY determines the length of the circadian period in Neurospora crassa. Embo j. 2001; PMC125781. doi:10.1093/emboj/20.24.7074. Görl, M., Merrow, M., Huttner, B., Johnson, J., Roenneberg, T. and Brunner, M. (2001)

Circadian regulation of the light input pathway in Neurospora crassa. Embo j. 2001; PMC133466. doi:10.1093/emboj/20.3.307. Merrow, M., Franchi, L., Dragovic, Z., Görl, M., Johnson, J., Brunner, M., Macino, G. and Roenneberg, T. (2001)

Modular structure of the TIM23 preprotein translocase of mitochondria. J Biol Chem. 2001; doi:10.1074/jbc.M102132200. Milisav, I., Moro, F., Neupert, W. and Brunner, M. (2001)

Role of the deafness dystonia peptide 1 (DDP1) in import of human Tim23 into the inner membrane of mitochondria. J Biol Chem. 2001; doi:10.1074/jbc.M105313200. Rothbauer, U., Hofmann, S., Mühlenbein, N., Paschen, S. A., Gerbitz, K. D., Neupert, W., Brunner, M. and Bauer, M. F. (2001)

Mechanisms of mitochondrial protein import. Protoplasma. 2000; doi:10.1007/BF01280499. Bauer, M. F., Paschen, S., Neupert, W. and Brunner, M. (2000)

Protein translocation into mitochondria: the role of TIM complexes. Trends Cell Biol. 2000; doi:10.1016/s0962-8924(99)01684-0. Bauer, M. F., Hofmann, S., Neupert, W. and Brunner, M. (2000)

The cytochrome bc1 and cytochrome c oxidase complexes associate to form a single supracomplex in yeast mitochondria. J Biol Chem 275, 18093-18098.
Cruciat, C. M., Brunner, S., Baumann, F., Neupert, W., and Stuart, R. A. (2000)

The role of the TIM8-13 complex in the import of Tim23 into mitochondria. Embo j. 2000; PMC305865. doi:10.1093/emboj/19.23.6392. Paschen, S. A., Rothbauer, U., Káldi, K., Bauer, M. F., Neupert, W. and Brunner, M. (2000)

Tim23 links the inner and outer mitochondrial membranes. Cell. 2000; doi:10.1016/s0092-8674(00)80850-8. Donzeau, M., Káldi, K., Adam, A., Paschen, S., Wanner, G., Guiard, B., Bauer, M. F., Neupert, W. and Brunner, M. (2000)


The mitochondrial TIM22 preprotein translocase is highly conserved throughout the eukaryotic kingdom. FEBS Lett. 1999; doi:10.1016/s0014-5793(99)01665-8.
Bauer, M. F., Rothbauer, U., Mühlenbein, N., Smith, R. J., Gerbitz, K., Neupert, W., Brunner, M. and Hofmann, S. (1999)

Assignment of circadian function for the Neurospora clock gene frequency. Nature. 1999; doi:10.1038/21190. Merrow, M., Brunner, M. and Roenneberg, T. (1999)

Genetic and structural characterization of the human mitochondrial inner membrane translocase. J Mol Biol. 1999; doi:10.1006/jmbi.1999.2751. Bauer, M. F., Gempel, K., Reichert, A. S., Rappold, G. A., Lichtner, P., Gerbitz, K. D., Neupert, W., Brunner, M. and Hofmann, S. (1999)

The TIM17.23 preprotein translocase of mitochondria: composition and function in protein transport into the matrix. Embo j. 1999; PMC1171444. doi:10.1093/emboj/18.13.3667. Moro, F., Sirrenberg, C., Schneider, H. C., Neupert, W. and Brunner, M. (1999)

Tim9, a new component of the TIM22.54 translocase in mitochondria. Embo j. 1999; PMC1171126. doi:10.1093/emboj/18.2.313. Adam, A., Endres, M., Sirrenberg, C., Lottspeich, F., 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. 1999; PMC1171402. doi:10.1093/emboj/18.12.3214. Endres, M., Neupert, W. and Brunner, M. (1999)


Carrier protein import into mitochondria mediated by the intermembrane proteins Tim10/Mrs11 and Tim12/Mrs5. Nature. 1998; doi:10.1038/36136.
Sirrenberg, C., Endres, M., Fölsch, H., Stuart, R. A., Neupert, W. and Brunner, M. (1998)

Biogenesis of Tim23 and Tim17, integral components of the TIM machinery for matrix-targeted preproteins. Embo j. 1998; PMC1170504. doi:10.1093/emboj/17.6.1569. Káldi, K., Bauer, M. F., Sirrenberg, C., Neupert, W. and Brunner, M. (1998)

C- to N-terminal translocation of preproteins into mitochondria. Embo j. 1998; PMC1170998. doi:10.1093/emboj/17.22.6508. Fölsch, H., Gaume, B., Brunner, M., Neupert, W. and Stuart, R. A. (1998)

Fzo1p is a mitochondrial outer membrane protein essential for the biogenesis of functional mitochondria in Saccharomyces cerevisiae. J Biol Chem. 1998; doi:10.1074/jbc.273.32.20150. Rapaport, D., Brunner, M., Neupert, W. and Westermann, B. (1998)

Proteine auf Reisen. Einsichten 2, 14-17. Bauer, M. F., Künkele, K. P., Neupert, W. and Brunner, M. (1998)

Unfolding of preproteins upon import into mitochondria. Embo j. 1998; PMC1170997. doi:10.1093/emboj/17.22.6497. Gaume, B., Klaus, C., Ungermann, C., Guiard, B., Neupert, W. and Brunner, M. (1998)

Functional cooperation and stoichiometry of protein translocases of the outer and inner membranes of mitochondria. J Biol Chem. 1997; doi:10.1074/jbc.272.47.29963. Sirrenberg, C., Endres, M., Becker, K., Bauer, M. F., Walther, E., Neupert, W. and Brunner, M. (1997)

Yeast mitochondrial F1F0-ATPase: the novel subunit e is identical to Tim11. FEBS Lett. 1997; doi:10.1016/s0014-5793(97)00691-1. Arnold, I., Bauer, M. F., Brunner, M., Neupert, W. and Stuart, R. A. (1997)

Determinants in the presequence of cytochrome b2 for import into mitochondria and for proteolytic processing. Eur J Biochem. 1996; doi:10.1111/j.1432-1033.1996.00856.x. Klaus, C., Guiard, B., Neupert, W. and Brunner, M. (1996)

Import of carrier proteins into the mitochondrial inner membrane mediated by Tim22. Nature. 1996; doi:10.1038/384582a0. Sirrenberg, C., Bauer, M. F., Guiard, B., Neupert, W. and Brunner, M. (1996)

Protein import across the inner mitochondrial membrane. NATO ASI Series H96, 157-165. Schneider, H. C., Berthold, J., Bauer, M. F., Klaus, C., Neupert, W. and Brunner, M. (1996)

Role of Tim23 as voltage sensor and presequence receptor in protein import into mitochondria. Cell. 1996; doi:10.1016/s0092-8674(00)81320-3. Bauer, M. F., Sirrenberg, C., 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. 1996; PMC452327. Schneider, H. C., Westermann, B., Neupert, W. and Brunner, M. (1996)

Dissection of protein translocation across the mitochondrial outer and inner membranes. Cold Spring Harb Symp Quant Biol. 1995; doi:10.1101/sqb.1995.060.01.066. Brunner, M., Schneider, H. C., Lill, R. and Neupert, W. (1995)

Purification and characterization of mitochondrial processing peptidase of Neurospora crassa. Methods Enzymol. 1995; doi:10.1016/0076-6879(95)48048-x. Brunner, M. and Neupert, W. (1995)

The MIM complex mediates preprotein translocation across the mitochondrial inner membrane and couples it to the mt-Hsp70/ATP driving system. Cell. 1995; doi:10.1016/s0092-8674(05)80013-3. Berthold, J., Bauer, M. F., Schneider, H. C., Klaus, C., Dietmeier, K., Neupert, W. and Brunner, M. (1995)

Characterization of the mitochondrial processing peptidase of Neurospora crassa. J Biol Chem 269, 4959-4967.
Arretz, M., Schneider, H., Guiard, B., Brunner, M., and Neupert, W. (1994)

Efficient but aberrant cleavage of mitochondrial precursor proteins by the chloroplast stromal processing peptidase. Eur J Biochem 221, 523-528.
Bassham, D. C., Creighton, A. M., Arretz, M., Brunner, M., and Robinson, C. (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.
Brunner, M. and Whiteheart, S. W. (1994)

Mitochondrial Hsp70/MIM44 complex facilitates protein import. Nature. 1994; doi:10.1038/371768a0. Schneider, H. C., Berthold, J., Bauer, M. F., Dietmeier, K., Guiard, B., Brunner, M. and Neupert, W. (1994)

N-ethylmaleimide-sensitive fusion protein: a trimeric ATPase whose hydrolysis of ATP is required for membrane fusion. J Cell Biol. 1994; PMC2120109. doi:10.1083/jcb.126.4.945. Whiteheart, S. W., Rossnagel, K., Buhrow, S. A., Brunner, M., Jaenicke, R. and Rothman, J. E. (1994)

The mitochondrial processing peptidase. In Heijne, G (ed.) Signal Peptidases, RG Landes Comp, 73-86.
Brunner, M., Klaus, C. and Neupert, W. (1994)

Domain structure of an N-ethylmaleimide-sensitive fusion protein involved in vesicular transport. J Biol Chem 268, 2662-2666.
Tagaya, M., Wilson, D. W., Brunner, M., Arango, N., and Rothman, J. E. (1993)

SNAP family of NSF attachment proteins includes a brain-specific isoform. Nature 362, 353-355.
Whiteheart, S. W., Griff, I. C., Brunner, M., Clary, D. O., Mayer, T., Buhrow, S. A., and Rothman, J. E. (1993)

SNAP receptors implicated in vesicle targeting and fusion. Nature 362, 318-324. Söllner, T., Whiteheart, S. W., Brunner, M., Erdjument-Bromage, H., Geromanos, S., Tempst, P., and Rothman, J. E. (1993)

A multisubunit particle implicated in membrane fusion. J Cell Biol 117, 531-538.
Wilson, D. W., Whiteheart, S. W., Wiedmann, M., Brunner, M., and Rothman, J. E. (1992)

Soluble N-ethylmaleimide-sensitive fusion attachment proteins (SNAPs) bind to a multi-SNAP receptor complex in Golgi membranes. J Biol Chem 267, 12239-12243.
Whiteheart, S. W., Brunner, M., Wilson, D. W., Wiedmann, M., and Rothman, J. E. (1992)

ADP-ribosylation factor is a subunit of the coat of Golgi-derived COP-coated vesicles: a novel role for a GTP-binding protein. Cell 67, 239-253.
Serafini, T., Orci, L., Amherdt, M., Brunner, M., Kahn, R. A., and Rothman, J. E. (1991)

Promoter recognition and promoter strength in the Escherichia coli system. EMBO J 6, 3139-3144.
Brunner, M., and Bujard, H. (1987)

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

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

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Fax:
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