Shabih Shakeel laboratory

Research Overview

View Dr Shakeel's latest PubMed publications listing PubMed or Orcid.

Shakeel lab website

Understanding heterochromatin – the dark matter of the genome

The central dogma of molecular biology postulates that genetic information flows linearly from DNA, the faithfully maintained blueprint of life, into RNA, the intermediate messenger, onto functional proteins, the machinery of our cells.

DNA, however, is much more than a simple linear code; it is packaged into a complex three-dimensional dynamic structure called chromatin in which DNA is wrapped around proteins known as histones. The compact nature of these structures restricts accessibility to genes. Indeed, 97 per cent of our DNA is packaged as heterochromatin - the dark matter of the genome and is thus inactive at any one time.

Not much is understood about heterochromatin, but its malfunction leads to cancer, developmental defects and susceptibility to infectious diseases.

Our lab seeks to understand the fundamental principles behind the formation, regulation and repair of heterochromatin. We hope to use these insights to discover new druggable targets.

Staff

Dr Winnie Tan, Postdoctoral Fellow, BSc(Hons) Melbourne, PhD Melbourne

Lilian Wong, Research Assistant, BSc(Hons) Ontario PhD Melbourne

Collaborators

Dr Lori Passmore, MRC Laboratory of Molecular Biology, Cambridge, U.K.

Dame Carol Robinson, University of Oxford, Oxford, U.K.

Prof Juri Rappsilber, Technical University Berlin, Berlin, Germany

Associate Professor Andrew Deans, St Vincent Institute, Melbourne, Australia

Funding

Start up grants from WEHI and University of Melbourne.

Research Opportunities

This research project is available to PhD students, Honours students, Post Doctor Researchers to join as part of their thesis.
Please contact the Research Group Leader to discuss your options.

Research Outcomes

Twarock R, Dykeman EC, Stockley PG, White S, Barker A, Patel N, Butcher SJ, Shakeel S, Harris M, Stewart H. Anti-viral therapy. Application number PCT/GB2014/052696. Filling date: 05/09/2014. Publication date: 12/03/2015. Status: Abandoned. Replaced this patent.

Research Publications

  1. Alcon P, Shakeel S, Chen ZA, Rappsilber J, Patel KJ, Passmore LA. FANCD2-FANCI is a clamp stabilized on DNA by monoubiquitination of FANCD2 during DNA repair. Nat Struct Mol Biol. 2020. 27, 240-248 PMID: 32066963
  2. Farrell DP, Anishchenko I, Shakeel S, Lauko A, Passmore LA, Baker D, DiMaio F. Deep learning enables the atomic structure determination of the Fanconi Anemia core complex from cryoEM. IUCrJ. 2020. 7, 881-892 PMID: 32939280
  3. Laurinmaki P, Shakeel S, Ekstrom JO, Mohammadi P, Hultmark D, Butcher SJ. Structure of Nora virus at 2.7 A resolution and implications for receptor binding, capsid stability and taxonomy. Sci Rep. 2020. 10, 19675 PMID: 33184473
  4. Shakeel S, Rajendra E, Alcon P, O'Reilly F, Chorev DS, Maslen S, Degliesposti G, Russo CJ, He S, Hill CH et al. Structure of the Fanconi anaemia monoubiquitin ligase complex. Nature. 2019. 575, 234-237 PMID: 31666700
  5. Shakeel S, Dykeman EC, White SJ, Ora A, Cockburn JJB, Butcher SJ, Stockley PG, Twarock R. Genomic RNA folding mediates assembly of human parechovirus. Nat Comm. 2017. 8, PMID: 28232749
  6. Shakeel S, Westerhuis BM, Domanska A, Koning RI, Matadeen R, Koster AJ, Bakker AQ, Beaumont T, Wolthers KC, Butcher SJ. Multiple capsid-stabilizing interactions revealed in a high-resolution structure of an emerging picornavirus causing neonatal sepsis. Nat Comm. 2016. 7, 11387 PMID: 27435188
  7. Shakeel S, Westerhuis BM, Ora A, Koen G, Bakker AQ, Claassen Y, Wagner K, Beaumont T, Wolthers KC, Butcher SJ. Structural basis of human parechovirus neutralization by human monoclonal antibodies. J Virol. 2015. 89, 9571-9580 PMID: 26157123
  8. Pandurangan AP, Shakeel S, Butcher S, Topf M. Combined approaches to flexible fitting and assessment in virus capsids undergoing conformational change. J Struct Biol. 2014. 185, 427-439 PMID: 24333899
  9. Shakeel S, Seitsonen JJ, Kajander T, Laurinmaki P, Hyypiä T, Susi P, Butcher SJ. Structural and functional analysis of coxsackievirus A9 integrin alphavbeta6 binding and uncoating. J Virol. 2013. 87, 3943-3951 PMID: 23365426
  10. Seitsonen JJ, Shakeel S, Susi P, Pandurangan AP, Sinkovits RS, Hyvonen H, Laurinmaki P, Yla-Pelto J, Topf M, Hyypiä T et al. Structural analysis of coxsackievirus A7 reveals conformational changes associated with uncoating. J Virol. 2012. 86, 7207-7215 PMID: 22514349

Research Projects

This Research Group doesn't currently have any projects



Faculty Research Themes

School Research Themes

Cellular Imaging & Structural Biology, Molecular Mechanisms of Disease, Cancer in Biomedicine



Key Contact

For further information about this research, please contact Lab Head & Principal Research Fellow Dr Shabih Shakeel

Department / Centre

Biochemistry and Pharmacology

Unit / Centre

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