Research

A Summary of the Science in our Lab

The Molecular Machines that Organize Chromosomes

All functions of the genome depend on the dynamic three-dimensional architecture of chromosomes within the cell's nucleus. The aim of our research is to understand the fundamental mechanisms behind the machines that organize chromosomes.

A major aspect of our work is to uncover the molecular basis for the formation of mitotic chromosomes. This process, known as chromosome condensation, is a key step for the successful segregation of chromosomes during cell divisions. Insights into the general working principles will be of great importance to our understanding of how cells prevent the emergence of aneuploidies, which are hallmarks of most cancer cells and the leading cause of spontaneous miscarriages in humans.

The Condensin Complex

A central player in the formation of mitotic chromosomes is a conserved multi-subunit protein complex known as condensin. We are using a combination of biochemistry, cell biology and structural biology approaches to study condensin function in yeast and mammalian cells.

New Condensation Factors

Our knowledge of the inventory of proteins that drive chromosome condensation is still incomplete. To identify yet undiscovered condensation factors, we are using a microscopy-based quantitative chromosome condensation assay in live fission yeast cells.

 

Condensin complexes are built from a pair of Structural Maintenance of Chromosomes proteins (SMC2 and SMC4), a kleisin subunit, and two proteins that are composed of alpha-helical HEAT repeat motifs. The SMC subunits heterodimerize via a globular 'hinge' domain at one end of a long coiled coil. The kleisin subunit connects the two SMC ATPase 'head' domains at the other end of the coils to create a large ring-shaped structure.

We have discovered that condensin encircles chromosomal DNA within the ring. Our working hypothesis is that condensin uses this topological principle to link chromatin fibers.

We now want to understand how condensin rings are loaded onto DNA to generate chromosome linkages.

Our chromosome condensation assay measures the distance between two fluorescently marked chromosome regions simultaneously in large numbers of fission yeast cells as they go through mitosis. We then apply automated image analysis routines to extract quantitative condensation parameters from the time-lapse recordings. We have used this method to screen through a large number of mutants with the aim of identifying novel regulators of chromosome condensation. We are currently investigating the first candidate genes identified in our screen.

Group Members

Meet or join the Group


Former Technicians, Visitors and Undergraduate Students
Marta Walczak
2008-2009
Sarah Sternberger
2010
Christian Seybold
2010
PhD Student in Elmar Schiebel's Group, ZMBH Heidelberg, Germany
Annabelle Hoegl
2010-2011
PhD Student in Stephan Sieber's Group, TU Munich, Germany
Tom Kruitwagen
2010-2011
Alexander Komin
2011
Carmen Aguirre Hernandez
2011
PhD Student Barts Institute London, UK
Andrea Hruby
2012
Sascha Dehler
2012
MSc Student University of Marburg, Germany
Kasia Drzewika
2012
PhD Student in Frauke Melchior's Group, ZMBH Heidelberg, Germany
Maja Cohen
2012-2013
Dominique Koppenhoefer
2013
BSc Student University of Bielefeld, Germany
Maria Saez Garcia
2014
BSc Student Universidad Catolica de Valencia, Spain
Henry Bailey
2014-2015
BSc Student in Wyatt Yue's group, SGC Oxford, UK
Manoj Rathinaswamy
2015

Postdocs

We welcome applications from highly motivated scientists.

Requirements
  • PhD degree in the life sciences
  • High motivation
  • Strong interest in biological mechanisms
What to send
  • Your scientific interests and career goals
  • CV and list of publications
  • Contact details of up to three referees

PhD Students

Unfortunately we currently have no openings for PhD Students.

 
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Undergraduates

We sometimes can offer exciting BSc or MSc thesis projects.

Requirements
  • MSc Student or advanced BSc Student
  • Excitement about research
  • Minimum duration: 6 months (!)
What to send
  • Short motivation letter
  • CV and list of courses taken
  • Reference from one University Advisor

Publications

Work from our Group


Y Frosi and CH Haering
Control of chromosome interactions by condensin complexes
Current Opinion in Cell Biology (2015)
M Kschonsak and CH Haering
Shaping mitotic chromosomes: From classical concepts to molecular mechanisms
BioEssays (2015)
JK Heriche, JG Lees, I Morilla, T Walter, B Petrova, M Julia Roberti, MJ Hossain, P Adler, JM Fernandez, M Krallinger, CH Haering, J Vilo, A Valencia, JA Ranea, C Orengo, J Ellenberg
Integration of biological data by kernels on graph nodes allows prediction of new genes involved in mitotic chromosome condensation
Molecular Biology of the Cell 25 (2014): 2522-2536
I Piazza, A Rutkowska, A Ori, M Walczak, J Metz, V Pelechano, M Beck and CH Haering
Association of condensin with chromosomes depends on DNA binding by its HEAT-repeat subunits
Nature Structural & Molecular Biology 21 (2014): 560-568
S Cuylen, J Metz, A Hruby and CH Haering
Entrapment of chromosomes by condensin rings prevents their breakage during cytokinesis
Developmental Cell 27 (2013): 469-478
I Piazza, CH Haering* and A Rutkowska*
Condensin: crafting the chromosome landscape
Chromosoma 122 (2013): 175-190
CH Haering and A Losada
Understanding chromatin and chromosomes: from static views to dynamic thinking
EMBO Reports 14 (2013): 109-111
B Petrova, S Dehler, T Kruitwagen, J-K Heriche, K Miura and CH Haering
Quantitative analysis of chromosome condensation in fission yeast
Molecular & Cellular Biology 33 (2013): 984-998
CH Haering and R Jessberger
Cohesin in determining chromosome architecture
Experimental Cell Research 318 (2012): 1386-1393
A Rutkowska, CH Haering* and C Schultz*
A FlAsH-based cross-linker to study protein interactions in living cells
Angewandte Chemie Int Ed 50 (2011): 12655
B Petrova and CH Haering
Condensin engages chromatin
ChemBioChem 12 (2011): 2399
S Cuylen, J Metz and CH Haering
Condensin structures chromosomal DNA through topological links
Nature Structural & Molecular Biology 18 (2011): 894-901
S Cuylen and CH Haering
Deciphering condensin action during chromosome segregation
Trends in Cell Biology 21 (2011): 552-559
A Kurze, KA Michie, SE Dixon, A Mishra, T Itoh, S Khalid, L Strmecki, K Shirahige, CH Haering, J Löwe and K Nasmyth
A positively charged channel within the Smc1/Smc3 hinge required for sister chromatid cohesion
EMBO Journal 30 (2010): 364-378
S Cuylen and CH Haering
A new cohesive team to mediate DNA looping
Cell Stem Cell 7 (2010): 424-426
K Nasmyth and CH Haering
Cohesin: its roles and mechanisms
Annual Reviews in Genetics 43 (2009): 525-558
CH Haering
Foreword: the many fascinating functions of SMC protein complexes
Chromosome Research 17 (2009): 127-129
CH Haering
Keeping replicated chromatids together until mitosis
Molecular Themes in Eukaryotic DNA Replication, L. Cox, ED. (Royal Society of Chemistry) (2009)
CH Haering*, AM Farcas*, P Arumugam, J Metson and K Nasmyth
The cohesin ring concatenates sister DNA molecules
Nature 454 (2008): 297-301
P Arumugam*, T Nishino*, CH Haering*, S Gruber and K Nasmyth
Cohesin's ATPase activity is stimulated by the C-terminal Winged-Helix domain of its kleisin subunit
Current Biology 16 (2006): 1998-2008
K Nasmyth and CH Haering
The structure and function of SMC and kleisin complexes
Annual Reviews in Biochemistry 74 (2005): 595-648
CH Haering, D Schoffnegger, T Nishino, W Helmhart, K Nasmyth and J Löwe
Structure and stability of cohesin's Smc1-kleisin interaction
Molecular Cell 15 (2004): 951-964
CH Haering and K Nasmyth
Building and breaking bridges between sister chromatids
Bioessays 25 (2003): 1178-1191
P Arumugam, S Gruber, K Tanaka, CH Haering, K Mechtler and K Nasmyth
ATP hydrolysis is required for cohesin's association with chromosomes
Current Biology 13 (2003): 1941-1953
S Gruber*, CH Haering* and K Nasmyth
Chromosomal cohesin forms a ring
Cell 112 (2003): 765-777
CH Haering*, J Löwe*, A Hochwagen and K Nasmyth
Molecular architecture of SMC proteins and the yeast cohesin complex
Molecular Cell 9 (2002): 773-788
D Ivanov, A Schleiffer, F Eisenhaber, K Mechtler, CH Haering and K Nasmyth
Eco1 is a novel acetyltransferase that can acetylate proteins involved in cohesion
Current Biology 12 (2002): 323-328
CH Haering, TM Nakamura, P Baumann and TR Cech
Analysis of telomerase catalytic subunit mutants in vivo and in vitro in Schizosaccharomyces pombe
PNAS 97 (2000): 6367-6372

Gallery

Some impressions from our group's activities.