ΙΝΣΤΙΤΟΥΤΟ ΒΙΟΛΟΓΙΑΣ, ΦΑΡΜΑΚΕΥΤΙΚΗΣ ΧΗΜΕΙΑΣ & ΒΙΟΤΕΧΝΟΛΟΓΙΑΣ
 
  Ανάπτυξη Φαρμάκων
  Υπολογιστική Χημεία
  Μοριακή Ανάλυση
  Οργανική & Οργανομεταλλική Χημεία
  Φαρμακευτική Χημεία
  Δομική Βιολογία & Χημεία
  Μοριακή Ενδοκρινολογία
  Γονιδιακή Ρύθμιση
  Μοριακή και Κυτταρική Γήρανση
  Βιοϊατρικές Εφαρμογές
  Ολιστικές προσεγγίσεις στην υγεία
  Χημική Καρκινογένεση & Γεννετική Τοξικολογία
  Μεταβολική Μηχανική & Βιοπληροφορική
  Βιοτεχνολογία
  Ενζυμική και Συνθετική Βιοτεχνολογία
  Βιομιμητική & Νανοβιοτεχνολογία

 

 

Ενζυμική και Συνθετική Βιοτεχνολογία

Research Group

Permanent staff
Dr. Georgios Skretas, Research Assistant Professor
PhD in Chemical Engineering, Princeton University, USA

Dr. Theodoros G. Sotiroudis, Researcher Emeritus
PhD in Chemistry, National & Kapodistrian University of Athens, Greece

 

Research Associates

Post-doctoral research associates
Dr. Kalliopi Kostelidou, PhD in Biosciences, University of Birmingham, UK
Dr. Michael Fasseas, PhD in Agricultural Sciences, Agricultural University of Athens, Greece
Dr. Lakshmi Tripathi, PhD in Molecular Biology, Tsinghua University, China

PhD candidates
Dimitra Gialama, M.Sc. in Biochemistry, Imperial College London, UK
Dafni Delivoria, M.Sc. in Chemistry, Loughborough University, UK
Ilias Matis, M.Sc. in Chemistry, University of Edinburgh, UK
Dimitra Zarafeta, B.Sc. in Chemical Engineering, National Technical University of Athens, Greece
Stefania Panoutsou, M.Sc. in Molecular Biology and Pathology of Viruses, Imperial College London and St Mary’s Hospital, UK

Research assistants
Athanasios Lampropoulos, M.Sc. in Organismal Studies, Heidelberg University, Germany
Aliki Papakonstantinou, M.Sc. in Medical Biotechnology, Wageningen University, Netherlands

Undergraduate research assistants
Dimitris Kissas, School of Chemical Engineering, National Technical University of Athens, Greece

 

Research objectives

The main goal of the Laboratory of Enzyme & Synthetic Biotechnology is the development of engineered microbial cells with the ability to perform novel and complex functions by employing principles of Synthetic Biology. The lab utilizes simple organisms, such as the bacterium Escherichia coli, the yeasts Saccharomyces cerevisiae and Pichia pastoris, and the microalgae Spirulina platensis and Nannochloropsis as a “biological chassis” and seeks to evolve them into efficient “cell factories” for the production of valuable biotechnological products, and for the performance of industrially important processes, such as drug sensing and discovery, biotransformations etc. Genetic engineering techniques are applied in order to redesign and rearrange the genome of the organism of interest, while protein engineering approaches (directed protein evolution) are utilized so as to introduce novel functions in the cell. A key aspect of the work that is carried out is the design and development of high-throughput screening systems which are used to isolate the rare biomolecules and microbial strains that execute the desired function among large combinatorial libraries comprising hundreds of millions of variants. Another goal of the lab is the exploitation of the bioactive components of olives, olive oil and other Greek endemic plants for the development of new pharmaceutical and cosmetic products.

 

Indicative research projects currently underway


1. Discovery of potentially therapeutic compounds against protein misfolding diseases by applying principles of molecular evolution.

We are currently targeting the following diseases:
  • Alzheimer’s disease

According to the amyloid cascade hypothesis, the misfolding and aggregation of the amyloid β peptide (Αβ) leads to the formation of oligomers and higher order aggregates which are highly toxic for certain kinds of human neurons. Conditions that favor the accumulation of these toxic protein species in the human brain, such as the presence of genetic mutations, toxic chemicals, ageing etc., result in extensive neuronal degeneration and death with subsequent development of Alzheimer’s disease (AD). Compounds with the ability to bind to Αβ and inhibit the formation of neurotoxic species have the potential to become therapeutic agents against AD.

 

  • Amyotrophic lateral sclerosis (ALS) caused by inherited/acquired genetic mutations in the gene encoding for the human enzyme Cu/Zn superoxide dismutase 1 (SOD1)
  • Parkinson’s disease
  • Certain forms of cancer caused by inherited/acquired genetic mutations that cause thermodynamic destabilization, misfolding and inactivation of the human tumor suppressor p53

Crystal structure of the complex of the DNA-binding domain of the human tumor suppressor p53 with a target DNA sequence. Mutations located far away from the DNA-binding site at amino acid residues V143, Y220, F270, and others destabilize the protein thermodynamically and cause misfolding and inactivation of the pro-apoptotic actions of the protein, leading to carcinogenesis. Small molecules with the ability to bind to and stabilize mutant p53 can rescue its apoptotic-promoting ability and serve as anti-cancer agents.

 

 

 

 

 

2. Development of novel protein-based tools for synthetic biology applications.

3. Engineering bacteria for the production of toxic membrane proteins in high yields.

4. Discovery of thermostable hydrolytic enzymes of industrial interest using metagenomic approaches and directed evolution.

 

5. Studies of the biologically active proteins and metabolites of Spirulina and of plants of the Greek flora.

Crithmum maritimum

Olea Europaea . Olive fruits

 

Microscopic view of Spirulina platensis cultured in our laboratory

 

Crithmum maritimum. A perennial halophyte native in Greece. Plant seed oil is suitable for the production of biodiesel

Recent Publications

Sotiroudis, T.G. and Sotiroudis G.T. 2013. Health aspects of Spirulina (Arthrospira) microalga food supplement. Journal of the Serbian Chemical Society. 78, 395-405.

Kyriazi, A., Papadimitriou, V., Sotiroudis, T.G. and Xenakis, A.  2013. Development and characterization of a digestion model based on olive oil microemulsions. European Journal of Lipid Science and Technology. 115, 601-611.  

Papadimitriou, V., Dulle, M., Wachter, W., Sotiroudis, T.G., Glatter, A. and Xenakis, A. 2013. Structure and Dynamics of Veiled Virgin Olive Oil: Influence of Production Conditions and Relation to its Antioxidant Capacity. Food Biophysics. 8, 112-121.

Skretas, G., and Kolisis, F.N. 2012. Combinatorial approaches for inverse metabolic engineering applications. Computational and Structural Biotechnology Journal. 3(4).

Skretas, G., Makino, T., Varadarajan, N., Pogson, M., and Georgiou, G. 2012. Multi-copy genes that enhance the yield of mammalian G protein-coupled receptors in Escherichia coli. Metabolic Engineering. 14(5):591-602

Parages, M.L., Rico, R.M.,   Abdala-Díaz, R.T., Chabrillón, M., Sotiroudis, T.G. and Jiménez, C. (2012) Acidic polysaccharides of Arthrospira (Spirulina) platensis induce the synthesis of TNF-α in RAW macrophages. Journal of Applied Phycolology. 24, 1537-1546.

Makino, T., Skretas, G. and Georgiou, G. 2011. Strain engineering for improved expression of recombinant proteins in bacteria. Microbial Cell Factories. 10(1):32 * *Characterized as “Highly Accessed”

Makino, T., Skretas, G., Kang, T.H., and Georgiou, G. 2011. Comprehensive engineering of Escherichia coli for enhanced expression of IgG antibodies. Metabolic Engineering. 13(2):241-51.

Skretas, G., and Georgiou, G. 2009. Genetic analysis of G protein-coupled receptor expression in Escherichia coli: Inhibitory role of DnaJ on the membrane integration of the human central cannabinoid receptor, Biotechnology and Bioengineering. 102(2) : 357-367
*“Editors’ choice” article

Skretas, G., and Georgiou, G. 2008. Engineering G protein-coupled receptor expression in bacteria. Proceedings of the National Academy of Sciences USA. 105(39) : 14747-14748

Skretas, G., Meligova, A., Villalonga-Barber, C., Mitsiou, D.J., Alexis, M.N., Micha-Screttas, M., Steele, B.R., Screttas, C.G., and Wood, D.W. 2007. Engineered chimeric enzymes as facile tools for pharmaceutical discovery: Construction of simple bacterial screens for the detection, discovery and assessment of estrogen receptor modulators. Journal of the American Chemical Society. 129 : 8443-8457
*This work has been featured in a number of press releases: 
http://www.sciencedaily.com/releases/2007/07/070718163719.htm
http://www.princeton.edu/engineering/news/publications/equad-news/s07/articles/foh.xml?id=559
http://it.moldova.org/news/engineered-e-coli-may-lead-to-new-drugs-59688-eng.html

Skretas, G., and Wood, D.W. 2005. A bacterial biosensor of endocrine modulators. Journal of Molecular Biology. 349: 464-474.
*Selected as an Article of Outstanding Interest by “Faculty of 1000”

Skretas, G., and Wood, D.W. 2005. Regulation of protein activity with small-molecule-controlled inteins. Protein Science.  14: 523-532.    

 

Patents

Wood, D.W. and Skretas, G. Bacterial ligand-binding sensor. United States Patent 7592144

 

Research funding

2015. Ioannis Latsis Foundation – Scientific Project Award. Project title: “Protein tools for programming cell behavior in synthetic biology”. Coordinator: Dr. Georgios Skretas. Total budget: 12,000 €. Lab budget: 12,000 €.

2013-2015. IKY Fellowships of Excellence for Postgraduate Studies in Greece- Siemens Program. Coordinator: Dr. Georgios Skretas. Post-graduate research fellow: Dr. Kalliopi Kostelidou. Total budget: 40,000 €. Lab budget: 40,000 €.

2013-2015. General Secretariat of Research and Technology – KRIPIS Grant. Project acronym: “STHENOS”. Coordinator: Dr. Alexandros Pintzas. Total budget: 1,500,000 €. Lab budget: 67,000 €.

2013. Ioannis Latsis Foundation – Scientific Project Award. Coordinator: Dr. Niki Chondrogianni. Total budget: 12,000 €. Lab budget: 6,000 €.

2012-2015. General Secretariat of Research and Technology – “ARISTEIA” Award. Project Acronym: “NEUROTHERAPY”. Coordinator: Dr. Georgios Skretas. Budget: 216.000 €. Lab Budget: 190,000 €.

2012-2015. Ministry of Education, Lifelong Learning, and Religious Affairs - Program “Thalis”. Project Acronym: “CYCLIPAD”. Coordinator: Dr. Efstathios Gonos. Budget: 540.000 €. Lab Budget: 171,000 €. 

2011-2015. FP7 European Union Cooperation Program KBBE-2010.3.5-04 - Microbial diversity and metagenomic mining for biotechnological innovation. Project Acronym: “HotZyme”. Coordinator:  Prof. Xu Peng, University of Copenhagen, Denmark. Total budget: 5,518,544 €. Lab budget (through the National Technical University of Athens): € 160,000. Website: hotzyme.com

2011-2015. European Union FP7 Marie Curie International Reintegration Grant. Project Acronym: “DEVOCAT”. Coordinator: Dr. Soterios Kyrtopoulos. Marie Curie Fellow: Dr. Georgios Skretas. Total budget: € 100,000. Lab budget: € 100,000. Website: http://www.eie.gr/nhrf/institutes/ibrb/eu-projects/DEVOCAT_project.pdf

2011-2015. General Secretariat of Research and Technology (Greece) Cooperation Program – Large Scale Cooperative Projects. Project Acronym: “DAMP”. Coordinator: Prof. Nektarios Aligiannis. Total budget: 1,412,000 €. Lab budget: € 150,000.

 

Participation in International Scientific Networks

COST Action BM1307 | European network to integrate research on intracellular proteolysis pathways in health and disease (PROTEOSTASIS) | 25 April 2014 - 24 April 2018. Dr. Georgios Skretas is serving as the 1st substitute Management Committee member for Greece.

COST Action CM1303 | Systems Biocatalysis (SysBioCat) | 20 November 2013 - 19 November 2017. Dr. Georgios Skretas is serving as the 1st substitute Management Committee member for Greece.

 

 

 

 

 
       

 

 

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