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Gene Regulation: Benjamin Rowland

Rowland Benjamin Liggend

Benjamin RowlandGroup Leader

About Benjamin Rowland

Shaping the genome in interphase and mitosis

Cells are only a few micrometers in size, yet each cell harbours our entire genome. These meters of DNA need to be organized in 3D to control many important cellular events. Both cohesin and condensin are so-called SMC complexes that by building DNA loops, and by holding together DNA elements, can provide structure to chromosomes.

Building chromatin loops in interphase

Cohesin plays a major role in the 3D organization of the interphase genome as it loops together regulatory elements along chromosomes. We recently found that such DNA loops can be increased in size, and that the duration with which cohesin entraps DNA determines the degree to which loops are enlarged. Our results therefore support the model that cohesin provides structure to the genome through the formation and processive enlargement of loops. This mechanism is referred to as loop extrusion. Cohesin has a dynamic mode of DNA binding that involves a cycle of DNA entrapment and WAPL-mediated DNA release. This allows for a constant cycle of the formation, enlargement, loss, and re-formation of loops that keeps the interphase genome dynamic.

Holding together the sister chromatids

In addition to its role in building loops, cohesin also holds together the sister chromatids of each chromosome. From DNA replication onwards, cohesin co-entraps the sister DNAs inside its ring-shaped structure, and cohesin holds together these sisters until mitosis. Cohesin then resists the pulling forces of microtubules until all chromosomes are correctly aligned at the metaphase plate. The abrupt cleavage of cohesin rings then triggers the synchronous segregation of sister chromatids to the opposite poles of the cell.

Mitotic chromosome condensation

As cells enter mitosis, condensin complexes convert the genome into compact and rigid chromosomes. Condensin drives chromosome condensation through the formation of loops along the DNA. This vital process ensures that chromosomes are shortened enough to allow the splitting in half of the cell during cytokinesis without DNA getting caught in the middle. Cohesin and condensin therefore both have an essential role in mitosis that ensures that each of the daughter cells receives an equal karyotype during cell division.

Research questions

Our research centres on the mode of action of cohesin and condensin. How do these complexes form DNA loops and shape the genome in 3D? How do these complexes entrap and release DNA? How does cohesin stably lock together the sister chromatids? How does condensin drive mitotic chromosome condensation? And how does loop formation by these complexes affect nuclear organization and gene expression? These are the kind of questions that keep us awake at night and drive our research. We are addressing such questions using a multi-disciplinary approach that involves genetics, genomics, biochemistry and imaging.

For more info about our research, check out our website.

Chromosomes for dummies

If you are not a scientist, but would like to know about our research, then watch Benjamin explain cell division and chromosomes (in Dutch):

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Positions available

We are recruiting. We have Postdoc, PhD student, Technician and Master student positions available. If you are interested in joining our lab, please send an enquiring email including your CV and motivation to Benjamin Rowland (b.rowland AT nki.nl).

Research in our lab is supported by the European Research Council (ERC), the Dutch Cancer Society (KWF), and the Netherlands Organisation for Scientific Research (NWO).

Co-workers

Haarhuis, Judith.jpg

Judith Haarhuis

Associate Staff Scientist

Experience

During my study Cancer, Genomics and Developmental Biology at Utrecht University I went for an intership to the group of prof. dr. K. Cimprich at Stanford University to study DNA Damage in Xenopus extracts.

After that I joined the lab of Benjamin Rowland as a PhD student. Here I study how sister chromatid cohesion is being regulated during cell division using yeast and human cell lines as a model organism.

See Judith's publications on PubMed

See also: Judith Haarhuis wins Antoni van Leeuwenhoek Award.

 

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Baldi, Giorgio

Giorgio Baldi

Postdoctoral Fellow

Experience

I took my master's degree in medical biotechnology and nanobiotechnology at the University of Salento (Italy). During this period, I met Professor Costanzo and, shortly after, I started my PhD in his group at IFOM, Milan. There, I gained expertise in DNA replication and visualization of peculiar DNA structures by atomic force microscopy and electron microscopy, dissecting the role of homologous recombination proteins.
In 2019 I joined Benjamin Rowland's lab where I study the cohesin complex and its interactors. I focus on post-translational modifications of these factors and on how this can impact chromatin organization.

See Giorgio's publications on PubMed.

 

 

 

 

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Virginie Roure

Virginie Roure

Postdoctoral Fellow

Experience

I did my PhD in the laboratory of Giacomo Cavalli at the Institute of Human Genetics in Montpellier, France. I studied the role of Polycomb and trithorax group proteins in the nuclear organization of their target Hox genes in Drosophila. During my postdoc, I worked on the epigenetic regulation of centromere identity in the laboratory of Patrick Heun at the Wellcome Centre for Cell Biology in Edinburgh, Scotland. In 2020 I joined the lab of Benjamin Rowland as a postdoc to explore the role of cohesin and condensin in chromosome organization.

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Garcia Nieto, Alberto

Alberto García Nieto

PhD Student

Experience

During my Master studies in Human Biology at the University of Copenhagen, I had the opportunity to work with Anja Groth, understanding the histone replication machinery.
In 2017, I started my PhD in the group of Benjamin Rowland. My project focusses on understanding how two independent processes, cohesion, and condensation, are coordinated in order to form the typical X-shape chromosome. My main interest lies in understanding how condensin is regulated and how this complex compacts chromatin. Besides, how cohesin is kept in this cohesive state and how it prevents unwanted segregation defects during mitosis are some of the questions I am trying to address.

See Alberto's publications on PubMed.

 

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Hoenkamp Claire

Claire Hoencamp

PhD Student

Experience

During my Master's in Oncology at the University of Amsterdam I did my first internship in Benjamin Rowland's lab at the NKI. My second internship took place in Michele Pagano's lab at New York University, after which I came back to the NKI to start my PhD in 2018, being enthused and inspired by the work performed in the Rowland lab.
In the Rowland lab we are excited to unravel the mysteries surrounding condensin and cohesin and their roles during the cell cycle. Specifically, during my PhD project I will focus on the condensin complex and its role during interphase.

See Claire's publications on PubMed.

See also: Claire Hoencamp receives competitive fellowship.

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van Ruiten, Marjon

Marjon van Ruiten

PhD Student

Experience

In 2016 I started my PhD in the group of Benjamin Rowland. I study how cohesin forms chromatin loops and mediates sister chromatid cohesion using a mammalian cell system. More specifically, I am interested to understand the role of cohesin acetylation in regulating cohesin-mediated processes. To support my research project, I received a PhD fellowship from the Boehringer Ingelheim Fonds.
I earned my Master's degree in Biomedical Sciences at Utrecht University, where I was enrolled in the program "Cancer, Stem Cells and Developmental Biology". I performed my first internship in the lab of Benjamin Rowland. My second internship took place in the lab of David Langenau at Massachusetts General Hospital, Boston.

See Marjon's publications on PubMed.

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Oldenkamp, Roel

Roel Oldenkamp

PhD student

Experience

During my master's program Molecular Mechanisms of Disease at the Radboud University in Nijmegen, I developed a strong interest in chromosome organization. Therefore, I joined the group of Benjamin Rowland in August 2018. As a group, we are mainly focused on the role of SMC complexes in shaping and maintaining the (3D) genome.

During my PhD, I try to understand molecular mechanisms that underlie cohesin-mediated interphase genome organization. Besides, I study the transition from highly dynamic G1 cohesin to relatively stable G2 cohesin.

See Roel's publications on PubMed.

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Sedeño Cacciatore

Ángela Sedeño Cacciatore

PhD Student

Experience

Shortly after graduating in Biotechnology at the University of Zaragoza, I started my Master's in Cancer, Stem cells and Developmental Biology at Utrecht University. I did my first masters internship in the lab of Sander van den Heuvel, investigatingSwi/Snf regulators in C. elegans. During my masters, I developed an interest in bioinformatics and joined the group of Jeroen de Ridder for my second internship. Here I used bioinformatics tools to explore MC-4C data. 
Throughout this period I grew an interest in how the genome is regulated and organized within the nucleus. To pursue this interest, in 2018 I started my PhD in the group of Benjamin Rowland. Here I use bioinformatics to look into how cohesin, condensin and their regulators act to organize the genome within confined borders.

See Angela's publications on PubMed.

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Willems

Laureen Willems

Technician

Experience

I graduated from Saxion University of Applied Sciences with a bachelor's degree in Biology and Medical Laboratory Research. During my bachelor's, I completed two internships, one in the lab of dr. H.A. Stenmark at the Norwegian Radium Hospital and in the lab of dr. F.A. Ossendorp at LUMC. Now, I will join the lab of Benjamin Rowland as a research technician.

See Laureen's publications on PubMed.

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Demi van Gent

Démi van Gent

Technician

Experience

I graduated from the University of Amsterdam with a Master's degree in Biomedical Sciences. During my Master,  I did two internships: one at the AMC in the lab of Hans Waterham, working on peroxisomal disorders, and one at the NKI in the lab of Reuven Agami, working on the role of p53 in senescence. In 2019 I joined the Rowland lab to work as a technician.

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Kyah van Megesen

Kyah van Megesen

master student

Experience

I did my Bachelor Biomedical Science at the University of Amsterdam, and through my Research Honours, I did an internship at the Van Amerongen Lab studying gene enhancers. For this, I analyzed topologically associated domains and learned more about how genome organization influences gene regulation. Now I have started with my Master's in Oncology at the University of Amsterdam, and here at Benjamin Rowland's lab, my project focusses on how SWI/SNF controls Cohesin loading and how this affects sister chromatid cohesion and 3D genome organization.

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Harriet Treurniet

Harriët Treurniet

undergraduate student

Experience

During my master's program Nanobiology I became interested in chromosome organization and gene regulation.
During my internship at the NKI I will look how the genome is shaped by condensin.

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Research updates View All Updates

  • ERC Consolidator Grant awarded to Benjamin

    Benjamin was recently awarded a prestigious ERC Consolidator Grant to investigate the mechanism by which cohesin structures interphase chromosomes.

    Check out the interview with Benjamin.

  • Judith Haarhuis wins the AVL Award

    Judith has won the Antoni van Leeuwenhoek Award 2017 for her fundamental discoveries in chromosome biology. This coveted prize is awarded to the most talented postdoc or PhD student of the previous year.

    Check out the interview with Judith.

Key publications View All Publications

  • The cohesin release factor WAPL restricts chromatin loop extension

    Cell 2017 May 4;169(4):693-707

    Haarhuis JH, van der Weide RH, Blomen VA, Yáñez-Cuna JO, Amendola M, van Ruiten MS, Krijger PH, Teunissen H, Medema RH, van Steensel B,  Brummelkamp TR, de Wit E, Rowland BD

    Link to Pubmed
  • Cohesin releases DNA through asymmetric ATPase-driven ring opening

    Mol. Cell 2016; 61:575-588

    Elbatsh AM, Haarhuis JH, Petela N, Chapard C, Fish A, Celie PH, Stadnik M, Ristic D, Wyman C, Medema RH, Nasmyth K, Rowland BD

    Link to Pubmed
 
 

Recent publications View All Publications

  • The structural basis for cohesin-CTCF anchored loops.

    Nature, 2020, Advance online

    Li Y, Haarhuis JHI, Sedeño Cacciatore Á, Oldenkamp R, van Ruiten MS, Willems L, Teunissen H, Muir KW, de Wit E, Rowland BD, Panne D.

    Link to Nature
  • Distinct roles for condensin’s two ATPase sites in chromosome condensation.

    Mol Cell 2019;76:724-737

    Elbatsh AMO, Kim E, Eeftens JM, Raaijmakers JA, van der Weide RH, García-Nieto A, Bravo S, Ganji M, uit de Bos J, Teunissen H, Medema RH, de Wit E, Haering CH, Dekker C, Rowland BD.

    Link to Pubmed
 

Contact

  • Office manager

    Suzanne Corsetto

  • E-mail

    s.corsetto@nki.nl

  • Telephone Number

    +31 20 512 1970

Suzanne Corsetto

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