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Unraveling the fascinating world of molecular machines with cryogenic electron microscopy

I am a postdoctoral researcher in the Klinge lab at The Rockefeller University in New York City. My primary research interests lie in deciphering the molecular basis underlying the assembly and quality control of giant nucleoprotein complexes involved in gene expression using structural, biochemical and cellular biology methods.

Research projects

DNA gyrase

Molecular architecture of type II DNA topoisomerases

Topoisomerases are large and complex machines consisting of multiple subunits that are involved in allosteric regulation of the DNA topology in all living cells. During my PhD research, I pursued the characterization of the bacterial DNA gyrase and human Topo IIa nucleoprotein complexes in presence of DNA and potent inhibitors to examine how these evolutionary related proteins have evolved their mechanism of action.

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Relevant publications:

  • Vanden Broeck A, Lotz C, Drillien R, Haas L, Bedez C, Lamour V. Structural basis for allosteric regulation of Human Topoisomerase IIa. (2021) Nature Communications 12 (2962), 1-13 


  • Vanden Broeck A, Lotz C, Ortiz J, Lamour V. Cryo-EM structure of the complete E. coli DNA gyrase nucleoprotein complex. (2019) Nature communications 10 (4935), 1-12​


  • Vanden Broeck A, Mc Ewen AG, Chebaro Y, Potier N, Lamour V. Structural basis for DNA gyrase interaction with Coumermycin-A1. (2019) Journal of Medicinal Chemistry 62 (8) 4225–4231.

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Nucleolar maturation of the human small subunit processome

Ribosomes, intricate RNA-protein molecular machines, catalyze protein synthesis in every living cell across all domains of life. In eukaryotes, the 80S ribosome comprises two subunits: the small subunit [SSU; 40S], which decodes messenger RNA, and the large subunit [LSU; 60S], responsible for peptide bond formation during protein synthesis. During my postdoctoral research, I was interested in uncovering how human cells assemble ribosomes. Particularly, using cryogenic electron microscopy, I investigated the early assembly of the human small ribosomal subunit at a structural and mechanistic level.

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Relevant publication:

  • Singh S †, Vanden Broeck A †*, Miller L, Chaker-Margot M, Klinge S*. Nucleolar maturation of the human small subunit processome. (2021) Science 373, eabj5338.  

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Principles of human pre-60S biogenesis

After working on the small ribosomal subunit, I investigated the nucleolar assembly and nuclear maturation of the human large ribosomal subunit. I used cryogenic electron microscopy to uncover the role of about 100 assembly factors and ribosomal proteins in catalyzing large subunit pre-rRNA folding across two sub-cellular compartments.

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Relevant publication:

  • Vanden Broeck A* & Klinge S*. Principles of human pre-60S biogenesis. (2023) Science 381, eadh3892

Divergent molecular machines in kinetoplastids

In my final year of postdoctoral research, I initiated a new research direction in which I aim to uncover the intriguing molecular realm of kinetoplastids.


Stay tuned!

Publications

†  co-first author  *  co-corresponding author

15.  Vanden Broeck A & Klinge S. Eukaryotic ribosome assembly. (2024) Annual Review of Biochemistry, 93:189–210

14.  Vanden Broeck A* & Klinge S*. Principles of human pre-60S biogenesis. (2023) Science 381, eadh3892.

13.  Sanghai Z, Piwowarczyk R, Vanden Broeck A, Klinge S. A co-transcriptional ribosome assembly checkpoint controls nascent large ribosomal subunit maturation. (2023) Nat Struct Mol Biol, 30, 594–599

12.  Singh S, Banerjee A, Vanden Broeck A, Klinge S. Rapid clonal identification of biallelic CRISPR/Cas9 knock-ins using SNEAK PEEC. (2023) Scientific Reports. 13, 1719.

11.  Wasmuth EV, Vanden Broeck A, LaClair JR, Hoover EA, Lawrence KE, Paknejad N, Pappas K, Matthies D, Wang B, Feng W, Watson PA, Zinder JC, Karthaus WR, de la Cruz JM, Hite JK, Manova-Todorova K, Yu Z, Weintraub ST, Klinge S, Sawyers CL. Allosteric interactions prime androgen receptor dimerization and activation. (2022) Molecular Cell 82 (11), 2021-2031

10.  Vanden Broeck A & Klinge S. An emerging mechanism for the maturation of the Small Subunit Processome. (2022) Current Opinion in Structural Biology Vol. 73, 102331

9.  Singh S †, Vanden Broeck A †*, Miller L, Chaker-Margot M, Klinge S*. Nucleolar maturation of the human small subunit processome. (2021) Science 373, eabj5338.  

8.  Zhu C, Guo X, Dumas P, Takacs M, Abdelkareem M, Vanden Broeck A, Saint-André C, Papai G, Crucifix C, Ortiz J, Weixlbaumer A. Transcription factors modulate RNA polymerase conformational equilibrium. (2022) Nature Communications. 13 (1546), 1-12

7.  Vanden Broeck A, Lotz C, Drillien R, Haas L, Bedez C, Lamour V. Structural basis for allosteric regulation of Human Topoisomerase IIa. (2021) Nature Communications 12 (2962), 1-13 

6.  Huang Shar-yin N, Michaels SA, Mitchell BB, Majdalani N, Vanden Broeck A, Canela A, Tse-Dinh YC, Lamour V, Pommier Y. Exonuclease VII repairs quinolone-induced damage by resolving DNA gyrase cleavage complexes. (2021) Science Advances 7 (10), eabe0384

5.  Vanden Broeck A, Lotz C, Ortiz J, Lamour V. Cryo-EM structure of the complete E. coli DNA gyrase nucleoprotein complex. (2019) Nature communications 10 (4935), 1-12​

4.  Vanden Broeck A, Mc Ewen AG, Chebaro Y, Potier N, Lamour V. Structural basis for DNA gyrase interaction with Coumermycin-A1. (2019) Journal of Medicinal Chemistry 62 (8) 4225–4231.

3.  Bedez C, Lotz C, Batisse C, Vanden Broeck A, Stote R, Howard E, Pradeau-Aubreton K, Ruff M, Lamour V. Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain (2018) Scientific Reports 8, 9272.

2.  Azarkan M, Feller G, Vandenameele J, Herman R, El Mahyaoui R, Sauvage E, Vanden Broeck A, Matagne A, Charlier P, Kerff F. Biochemical and structural characterization of a mannose binding jacalin-related lectin with two-sugar binding sites from pineapple (Ananas comosus) stem. (2018) Scientific Reports 8, 1150.

1.  Vanden Broeck A, Van der Heiden E, Sauvage E, Dauvin M, Joris B, Duez C. A Lysine Cluster in Domain II of Bacillus subtilis PBP4a Plays a Role in the Membrane Attachment of This C1- PBP. (2015) PLoS ONE 10(10): e0140082.

Illustrations portfolio

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Contact me

Arnaud Vanden Broeck

Postdoctoral Research Fellow

Rockefeller University

Klinge Laboratory

1230 York Avenue

New York

10065 NY

USA

avanden [at] rockefeller [dot] edu

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