Research Groups

Sibon group

The Sibon’s group focus is to understand Coenzyme A metabolism in health and disease. Coenzyme A is a central metabolic cofactor, known for over 60 years. In recent years, the awareness is increasing that Coenzyme A, in addition to its essential role in metabolism also plays a role in signal transduction, ageing, epigenetics and neurodegeneration.

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  • Ody Sibon Visit
    Position

    Professor, Principal Investigator

    Research fields

    Molecular and Cellular Biology

    Postdoctoral Fellows
    PhD Students
    Technicians
      • Selected Publications:
      1. Ody C.M. Sibon & Erick Strauss.  Coenzyme A: make  it or (re) uptake it. Nature Reviews in Molecular Cell Biology 2016 Oct;17(10):605-6  (pdf).
      1. SrinivasanB,  M.Baratashvili, S. Hayflick, C. Colombelli, M. Van der Zwaag, B. Kanon, O. Schaap, E.A.A. Nollen, V. Tiranti, A. Podgoršek, G. Kosec, H. Petković, D.J. Reijngoud, N.A. Grzeschik, Ody C.M. Sibon. Extracellular 4’-Phosphopantetheine is a stable and novel substrate for intracellular Coenzyme A synthesis. Nature Chemical Biology 2015 Oct;11(10):784-792. (pdf) 
      1. Brunetti D, Dusi S, Giordano C, Lamperti C, Morbin M, Marchet S, Fagiolari G, Sibon OCM, Moggio M, d’Amati G, and Tiranti V. Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a Pank2 knock-out mouse model. Brain  (2014) Jan: 137 (Pt 1): 57-68. (pdf) 
      1. Den Hoed M,….Sibon OCM*, et al. Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.  Nature Genetics 2013 Jun;45(6):621-31. *All included functional Drosophila melanogaster experiments of this GWAS study were chaired by Sibon OCM. (pdf)
      1. Rana A, Seinen E, Siudeja K, Muntendam R, Srinivasan B, van der Want J, Hayflick S, Reijngoud D, Kayser O, Sibon OCM. Pantethine rescues a Drosophila model for Pantothenate Kinase-Associated    Proc Natl Acad Sci U S A. 2010 107:6988-93. (pdf)
      1. Bosveld F, Rana A, van der Wouden P, Lemstra W, Ritsema M, Kampinga HH, Sibon OCM. De novo CoA biosynthesis is required to maintain DNA integrity during development of the Drosophila nervous system. Hum Mol Gen 2008 17:2058-69. (pdf)
      1. Hut HMJ, Lemstra W, Blaauw EH, van Cappellen GWA, Kampinga HH, Sibon OCM. Centrosomes split in the presence of impaired DNA integrity during mitosis. Mol Biol Cell. 2003 14:1993-2004. (pdf)
      1. Sibon OCM, Kelkar A, Lemstra W, Theurkauf WE. DNA-replication/DNA-damage-dependent centrosome inactivation in Drosophila embryos. Nat Cell Biol. 2000 2:90-5. (pdf)
      1. Sibon OCM, Laurencon A, Hawley R, Theurkauf WE. The Drosophila ATM homologue Mei-41 has an essential checkpoint function at the midblastula transition. Curr Biol. 1999 9:302-12. (pdf)
      1. Sibon OCM, Stevenson VA, Theurkauf WE. DNA-replication checkpoint control at the Drosophila midblastula Nature. 1997 388:93-7. (pdf)
       
  • PhD students:
    Hilda de Vries
    Ria Hut
    Floris Bosveld
    Xia Yi
    Erwin Seinen
    Katarzina Siudeja
    Anil Rana
    Balaji Srinivasan
    Marianne de Villiers
    Madina Baratashvili

  • The current view is that cells obtain their Coenzyme A via a de novo biosynthesis pathway starting with the uptake of vitamin B5. Recently the Sibon group showed that cells and organisms can also take up Coenzyme A from external sources. The mechanism behind this newly discovered manner of obtaining Coenzyme A is under investigation. The presence of this alternative route of intracellular Coenzyme A is of high importance for subjects suffering from inborn genetic errors of impaired Coenzyme A de novo biosynthesis, resulting in severe neurodegenerative diseases. Findings obtained in model organisms are being explored how to use external supplies of Coenzyme A to develop therapies for these diseases.

    Figure

    Figure 2

  • Ody C.M. Sibon received her PhD in 1994 in Molecular Cell Biology at the University of Utrecht, The Netherlands. She studied the topological organization of transcription and splicing at the ultrastructural level under the supervision of Prof. A.J. Verkleij. She then moved to the United States, were she studied the role of DNA checkpoint regulation during early embryonal development in Drosophila melanogaster at the University of Stoney brook, NY. Her postdoctoral advisor was prof. W.E. Theurkauf.

    In 1998 she moved to the University of Groningen, the Netherlands were she started her own group. In 2002 she received a VIDI grant and in 2011 a VICI grant, both from the Dutch organization for Scientific research. Her research now is focussed on understanding the mechanisms of an altered Coenzyme A uptake route and the possibilities of this route in health and disease. She is named as inventor on several patents based on her discoveries related to Coenzyme A metabolism and she is developing these further towards therapies for  Coenzyme A-related diseases. In 2009 she became a full professor. She is partner and/or coordinator of several European, American and Dutch grants.

  • See all dissertations supervised by Ody Sibon (promotor)

     

    Rescue strategies in Drosophila models of neurodegenerative diseases
    2016, Baratashvili,M.B. (Madina)
    BCN-BRAIN / MOLAR: Molecular Neuroscience and Ageing Research

    In the past decades advances in medicine have led to an extended life span of the general population, which, as a negative consequence, increased the occurrence of age-related neurodegenerative diseases. The necessity to improve the quality of life together with the urge to decrease the economic burden related to patients with neurodegenerative diseases, brings focus to the …

    » read more

    Rerouting ‘coenzyme A’ biosynthesis
    2015, Srinivasan,B. (Balaji)
    BCN-BRAIN / MOLAR: Molecular Neuroscience and Ageing Research

    » read more

    Coenzyme A as a central player in cellular and tissue homeostasis
    2012, Siudeja,K. (Katarzyna)
    GUIDE / NNOC: Northern Netherlands Oncology Centre

    More information in the catalogue More information in Picarta

    » read more

    Small regulatory RNAs: identification, classification and utilization
    2011, Seinen,E. (Erwin)
    GUIDE / NNOC: Northern Netherlands Oncology Centre

    Een belangrijk onderdeel binnen de (bio)wetenschap is onderzoek naar de functie van genen. Voorheen werd dat vooral gedaan door opzettelijk mutaties in genen te maken, waardoor uiteindelijk specifieke eiwitten fouten bevatten en niet goed werken. De consequenties van disfunctionerende eiwitten kunnen daarna bestudeerd worden in cellen of in modelorganismen. De geconstate…

    » read more

    The role of impaired De novo Coenzyne A biosynthesis in pantothenate kinase-associated neurodegeneration : insight from a Drosophila model
    2010, Rana,A. (Anil)
    GUIDE / NNOC: Northern Netherlands Oncology Centre

    Pantothenate kinase-associated neurodegeneration (PKAN, OMIM 234200) is an autosomal recessive, progressive neurodegenerative disorder. PKAN is caused by mutations in pantothenate kinase 2 (PANK2), the gene that encodes an enzyme (PANK2) which is a rate limiting enzyme in de novo Coenzyme A (CoA) biosynthesis. Interestingly, in humans there are four highly homologous PANK ge…

    » read more

  • Interesting websites linked to the Sibon lab

  • Student projects:

    • Understanding the uptake mechanism of Coenzyme A and its precursors from external sources.
    • Exploring the possibilities of patented compounds to treat Pantothenate Kinase-Associated Neurodegeneration.
    • Developing a Google-Drosophila tool to study the ultrastructure of the Drosophila brain

     

    You can apply via this application form.

  • Post doctoral fellow position available at the Sibon lab for the following project on the intersection between chemistry and cell biology (pdf). Application at the end of this page.

    Coenzyme A is an essential metabolic cofactor for living organisms and is mostly known for its role in over 100 cellular metabolic reactions. We and others demonstrated that Coenzyme A is also a key factor in protein modifications and signal transduction, further expanding the prominence of Coenzyme A in living organisms.
    Until very recently, the consensus has been that intracellular Coenzyme A is obtained exclusively by a universally conserved five-step, de novo biosynthesis pathway in the cytosol of each cell, which begins with the uptake of vitamin B5. Patients with an inborn-error of this pathway suffer from neurodegeneration. Recently, we have demonstrated that cells and organisms have an alternative strategy for obtaining Coenzyme A, which involves the uptake of extracellular Coenzyme A. In particular, we have shown that various eukaryotic cells and organisms convert Coenzyme A present in the environment extracellularly into 4’-phosphopantetheine. This metabolite is subsequently incorporated into cells and converted back into Coenzyme A. This project is aimed to investigate the physiological relevance of this discovery.
    Preliminary results using validated fruit fly models suggest a possible flow of Coenzyme A (precursors) between organisms, namely from mothers to progeny or from microflora to the host.
    By using these models and newly developed sensitive analytical detection methods for Coenzyme A and its precursors, the project aims to provide proof for intra-organismal flows of Coenzyme A. This research will change longstanding Coenzyme A concepts with possible impact on health and disease, especially for the treatment of inborn-errors of Coenzyme A biosynthesis.

    1) Sibon O.C.M. & Strauss E. Coenzyme A; to make it or uptake it. Nat Rev Mol Cell Biol 17, 605-606 (2016)
    2) Srinivasan B, Baratashvili M, Hayflick S, Colombelli C, Van der Zwaag M, Kanon B, Schaap O, Nollen E, Tiranti V, Podgoršek A, Kosec G, Petković H, Reijngoud D.J., Grzeschik N.A, Sibon O.C.M. Extracellular 4’-Phosphopantetheine is a stable and novel substrate for intracellular Coenzyme A synthesis. Nature Chemical Biology 2015 Oct;11(10):784-92)

    Position for 1 year with an extension of another 2 years.
    Candidates much have obtained their PhD and must have a strong publication record. A background in chemistry is preferable but not a requirement.

    Information: Ody Sibon: o.c.m.sibon@umcg.nl

    Application

    Post doc position Sibon Lab

    • Please write your motivation in the box below and upload your resume through the button below.
    • Drop files here or

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