Fungal Systems Biology

Summary of research activities
Fungal Systems Biology aims in for a better systems understanding in the scope of industrial and medical Biotechnology. Fungal Systems Biology has a strong background in filamentous fungal functional genomics, in particular in the field of Aspergilli. Filamentous fungi are characterized by their large biotransformation capacity. More specifically by their;

  • large protein secretion capacity,
  • high organic acid production capacity and
  • by their plant cell wall degradation capacity. These characteristics provide an excellent basis for both basic and applied research.
     

Systems biology of protein secretion in filamentous fungi
Systems Biology of protein secretion aims to unravel the basic principles involved underlying the high secretion capacity of filamentous fungi. Protein secretion is studied in a Systems Biology approach with emphasis on Structural Systems Biology using a sub-cellular proteomics analysis approach.

Projects
  1. Novel enzyme tools for production of functional oleochemicals from unsaturated lipids ERA-Industrial Biotechnology, 2009-2012, Coordinator Prof J. Buchert (VTT, Finland).
    Personnel involved: Ir. Ruud Heshof MSc (PhD student) and Dr. ir. Leo de Graaff
    The objective of the project is to develop enzyme-aided technologies for upgrading of low cost unsaturated fatty acids to functional oleochemicals to be used as coatings, adhesives, lubricants, plasticizers and natural plastics. The consortium consists of multidisciplinary expertise combining biotechnical expertise to chemical engineering and polymer technology. The consortium involves 2 research institutes, 3 universities and 1 industrial partner.
  2. Novel laccases and their enhanced expression in Aspergillus niger NWO IBOS project 2009-2011
    Personnel involved: Dr J.A Tamayo Ramos and dr.ir. Leo de Graaff (Projectleader)
    The project aims 1) to effectively produce multicopper enzymes (laccases) from Aspergillus niger to study their biological role and 2) to develop efficient protein production systems in A.niger on the basis of translation enhancers to use the enzymes a biocatalysts. The project is a collaboration with Proteonic, Leiden, the Netherlands.
     

Systems Biology of organic acid production in filamentous fungi
Organic acid production is one of the characteristic processes of filamentous fungi, most well-known is organic acid production by A. niger. Despite the long industrial application of A.niger for citric acid production, the mechanism underlying the process is not very well understood. A Systems Biology approach that takes the various cellular compartments into account might contribute in unravelling the mechanism(s) involved.

Projects
  1. Itaconic acid production in A. niger
    Personnel involved: dr.ir. Leo de Graaff
    The aim of the project is to investigate, model and engineer the Aspergillus niger metabolic pathways that are involved in the cost-efficient production of organic acids, in particular itaconic acid and fumaric acid. A substantial part of the project is to understand the metabolic mechanisms controlling the accumulation of carboxylic acids in A. niger. This fundamental work includes the i) identification of mechanisms involved and ii) the bottlenecks in the pathways leading to the over-production of itaconic acid and fumaric acid, iii) the identification of the sub-cellular compartments that play a role and iv) the identification of membrane bound carrier proteins.

       

Systems Biology of lignocellulose degradation in filamentous fungi
A third theme is the degradation of lignocellulose by filamentous fungi. The paradigm in this research has become the XlnR regulon as was first described by our group 12 years ago. The area can still be explored further since many aspects of the signalling pathways involved (specific induction, carbon catabolite repression) are still obscure.

Projects
  1. Modelling of genetic networks WU-VLAG, WU-IPOP 2008-2012 , collaboration with Systems Control, dr. A.J.B. van Boxtel (project leader)
    Personnel involved: J. Omony MSc, dr. ir. Leo de Graaff, dr. A.J.B. van Boxtel (project leader)
    The aims of this project are to improve current and to develop new methodology for the quantification of genetic networks with respect to 1) efficient identification of quantative relationships from limited datasets obtained by transcriptomics, 2) the automatic identification of network structures, 3) the improvement in network identification by perturbation studies.

 
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