New Feeling

Our Scientific Vision

Atheris is a research company. We like to be involved in projects adressing major human health issues. In view to our family owned and family driven model, our work is based on contract research sponsored by our customers and partners. Our scientific vision is not limited to laboratory work. We like to observe Nature, to learn from what it has to offer, to protect it and find a lot of inspiration in the frame of exploratory scientific expeditions we organise.

Although we would like to do more, we can afford only a limited effort on stringently selected internal programs. We have decided not to conduct any development in-house, as this is too demanding and would affect our way of life and probably take the lead in our activities. We like to stay a small and dynamic group, an inspired problem-solving and discovery team. This is why we like to partner or spin-off our discoveries at early stages. This was achieved already on two occasions and led to the creation of two emerging companies:

• Our work on enzymes secreted by pathogenic fungi went beyond expectations, which led us in 2005 to create FunZyme Biotechnologies S.A. with colleagues, family and friends. These proteases have unprecedented activities and offer a range of promising industrial applications.
  
  
• We have assisted the group of Prof. Daniel Bertrand from the Department of Neurosciences at the University Medical School in Geneva in the development and validation of high-througput automated robots for functional electrophysiology assays. HiQScreen SaRL was created in 2007 to exploit this promising technology.
  
  

Furthermore, the discovery of an original peptide in the venom of a cone snail was at the origin of CONCO - The cone snail genome project for health (see below).

All these adventures have further stimulated our entrepreneurial spirit. In 2008, we launched the production, selling and marketing of our product Melusine, a collection of pre-fractionated venoms and other natural extracts, ready-made for high-throughput screening in the frame of industrial drug discovery programs.

We also like to promote the exchange of scientific view, bring together decision makers and get them to interact and a warm and friendly atmosphere of our NP2D - Natural Peptides to Drugs congress, the fourth edition of which is already schedule for 2010.

Last but not least, the broad scientific vision and extremely ambitious venomics project that we designed with our friends André Ménez and Dietrich Mebs resulted in the creation of the non-profit Toxinomics Foundation.

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Scientific Projects

• Atheris is coordinator of CONCO - The cone snail genome project for health, an Integrated Project funded by the European Community and gathering 20 partners over 5 years with a budget of 10.7 million Euros for an ambitious project that aims at generating high added value.
  
  
• In collaboration with Prof. Oliver Hartley from the University Medical School in Geneva, with our spin-off company FunZyme BioTechnologies S.A. and with an industrial partner we work on an innovative technology known as covalent capture and couple it to the use of new proprietary enzymes to develop novel tools for peptide and protein purification.
  
  
• With our close friend Prof. Dietrich Mebs from the University of Frankfurt we have been working on several nice projects, such as a study on the venom of Osmia rufa, an interesting species of solitary bee. This allowed us to discover novel peptides with interesting antimicrobial activities. This work has just been accepted for publication.
  
  
• In the frame of an ambitious project on leukodystrophies, rare genetic disorders affecting the myelin in the brain, we have established original peptidomic strategies and developped biocomputing tools for the discovery, identification and follow-up of selective biomarkers in body fluids and other tissues.
  
  
• Within the same research project funded by the Foundation of the European Leukodystrophy Association, we have developped a simple, but efficent, quantitative assay to profile and measure levels of sulfatides in human blood plasma and urine. Sulfatides are important metabolites for a range of human disorders, and our bioanalytical method, which is based on mass spectrometry, offers a range of advantages. A manuscript is in preparation.
  
  
• With our long term friends at Pentapharm A.G. in Basel (which recently became a branch of DSM) and in the frame of the PhD thesis of Dr. Anna Perchuc, we have conducted an in depth investigation of the venom proteome of the Brazilian lancehead snake Bothrops moojeni. This has already led us to two publications, one in the field of hemostasis and the other covering bradykinin potentiating peptides (BPP), hypotensive molecules inhibiting the angiotensin converting enzyme that led to the discovery of Captopril, a major drug to treat hypertension.
  
  
• In the frame of IMMUNAQUA, an INCO-DEV Project supported by the European Community in which Atheris was main contractant (partner 4), we are rather proud to say that our efforts contributed to three scientific publications, one even in the prestigious Proceedings of the Natural Academy of Sciences (PNAS). Immunaqua was a great project dealing with peptidic anti-infectious immune effectors in marine invertebrates, their characterisation and application for disease control in aquaculture. This project led Atheris entering the field of marine biology, and we have established long term partnerhips that are partially shared in CONCO. All this will certainly lead us to additional successful stories.
  

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Recent Publications

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The following manuscripts have just been published or are in press:

• From venoms to drugs: introduction.
  Toxicon. Editorial, in press, (2012).
  Harvey, A.L. and Stöcklin, R.
  Recruitment of glycosyl hydrolase proteins in a cone snail venomous arsenal: further insights into biomolecular features of Conus venoms.
  Marine Drugs. 10:258-280, (2012).
  Violette, A., Leonardi, A., Piquemal, D., Terrat, Y., Biass, D., Dutertre, S., Noguier, F., Ducancel, F., Stöcklin, R., Križaj, I. and Favreau, P.
  A novel mu-conopeptide, CnIIIC, exerts potent and preferential inhibition of NaV1.2/1.4 channels and blocks neuronal nicotinic acetylcholine receptors.
  Brit. J. Pharmacol. In press, (2012).
  Favreau, P., Benoit, E., Hocking, E., Carlier, L., D’hoedt, D., Leipold, E., Markgraf, D., Schlumberger, S., Cordova, M., Gaertner, H., Paolini-Bertrand, M., Hartley, O., Tytgat, J., Heinemann, S., Bertrand, D., Boelens, R., Stöcklin, R. and Molgo, J.
  Identification and classification of conopeptides using profile Hidden Markov Models.
  Biochem. Biophys. Acta. 1824(3):488-492, (2012).
  Laht, S., Koua, D., Kaplinski, L., Lisacek, F. Stöcklin, R. and Remm, M.
  Future perspectives of venoms for drug discovery.
  Pharmanufacturing: The international peptide review. (Nov. 2011):21-24, (2011).
  Stöcklin, R. and Vorherr, T.
  High resolution picture of a venom gland transcriptome: case study with the marine snail Conus consors.
  Toxicon. 59(1):34-46, (2011).
  Terrat, Y., Biass, D., Dutertre, S., Favreau, P., Remm, M., Stöcklin, R., Piquemal, D. and Ducancel, F.
  Venom composition and strategies in spiders: is everything possible?
  Advances in Insect Physiology. 40:1-86, (2011).
  Kuhn-Nentwig, L., Stöcklin, R. and Nentwig, W.
  Bioinformatic challenges in DNA metabarcoding.
  Mol. Evol. In press, (2011).
  Coissac, E., Riaz, T. and Puillandre, N.
  Venomic study on cone snails (Conus spp.) from South Africa.
  Toxicon, 57(1):28-34, (2011).
  Kauferstein, S., Port, C., Kendel, Y., Wunder, C., Nicke, A., Kordis, D., Favreau, P., Koua, D., Stöcklin, R. and Mebs, D.

The following articles have recently been published:

• Sequencing the genome of Conus consors: preliminary results.
  E-book of the SFET (French Society on Toxinology, www.sfet.asso.fr) pp. 11-16 (2010).
  Stockwell, T., Baden-Tillson, H., Favreau, P., Mebs, D., Ducancel, F. and Stöcklin, R.
• New tools to discover active molecules in venoms : from theory to practice.
  E-book of the SFET (French Society on Toxinology, www.sfet.asso.fr) pp.55-62, (2010).
  Favreau, P., Neveu, E., Maver, M., Stöcklin, R. and Bertrand, D.
• CONCO, the cone snail genome project for health.
  E-book of the SFET (French Society on Toxinology, www.sfet.asso.fr) pp. 17-20, (2010).
  Bianchi, E., Favreau, P., Benoit, E., Molgo, J., Ducancel, F., Servent, D., Stockwell, T., Mebs, D., Ménez, R., Miljanich, G. and Stöcklin, R.
• Rapid intraspecimen evolution of cone snail venom composition : multiplying pharmacological profiles?
  E-book of the SFET (French Society on Toxinology, www.sfet.asso.fr) pp. 175-176, (2010).
  Biass, D., Dutertre, S., Favreau, P. and Stöcklin, R.
• Venomic study on cone snails (Conus spp.) from South Africa.
  Toxicon 57(1):28-34, (2010).
  Kauferstein, S., Port, C., Kendel, Y., Wunder, C., Nicke, A., Kordis, D., Favreau, P., Koua, D., Stöcklin, R. and Mebs, D.
• Venoms - a natural source for mini-protein drugs.
  Pharmanufacturing: The international peptide review (Sept.):44-46, (2010).
  Stöcklin, R. and Vorherr, T.
• Structural identification by mass spectrometry of a novel antimicrobial peptide from the venom of the solitary bee Osmia rufa (Hymenoptera: Megachilidae).
  Toxicon 55(1):20-27, (2010).
  Stöcklin, R., Favreau, P., Thai, R., Pflugfelder, J., Bulet, P. and Mebs, D.
• Dramatic intraspecimen variations within the injected venom of Conus consors: an unsuspected contribution to venom diversity.
  Toxicon 55(8):1453-62, (2010).
  Dutertre, S., Biass, D., Stöcklin, R. and Favreau, P.
• Isolation and characterization of two new Lys49 PLA2s with heparin neutralizing properties from Bothrops moojeni snake venom.
  Toxicon 55(6):1080-92, (2010).
  Perchuc, A.M., Menin, L., Favreau, P., Buehler, B., Bulet, P., Schöni, R., Wilmer, M., Ernst, B. and Stöcklin, R.
• Use of venom peptides to probe ion channel structure and function.
  J. Biol. Chem. 285(18):13315-20, (2010).
  Dutertre, S. and Lewis, R.J.
• Platelet-active substances in the venom of Bothrops moojeni snake-a novel evaluation method using whole blood aggregometry.
  Platelets. 21(1):20-8, (2010).
  Demler, C., Buehler, B., Menin, L., Stöcklin, R., Wilmer, M., Ernst, B. and Perchuc, A.M.
• Marine snail venoms : use and trends in receptor and channel neuropharmacology.
  Curr. Opin. Pharmacol. 9(5):594-601, (2009).
  Favreau, P.and Stöcklin, R.
• Comparative proteomic study of the venom of the piscivorous cone snail Conus consors.
  J. Proteomics 72(2):210-218, (2009).
  Biass, D., Dutertre, S., Gerbault, A., Menou, J.-L., Offord, R.E., Favreau, P. and Stöcklin, R.
• New conopeptides of the D-superfamily selectively inhibiting neuronal nicotinic acetylcholine receptors.
  Toxicon 54(3):295-301, (2009).
  Kauferstein, S., Kendel, Y., Nicke, A., Coronas, F.I., Possani, L.D., Favreau, P., Krizaj, I., Wunder, C., Kauert, G. and Mebs, D.
• High throughput screening of bradykinin-potentiating peptides in Bothrops moojeni snake venom using precursor ion mass spectrometry.
  Toxicon 51(7):1288-1302, (2008).
  Menin, L., Perchuc, A., Favreau, P., Perret, F., Michalet, S., Schöni, R., Wilmer, M. and Stöcklin R.
• Molecular characterisation of endogenous snake venom metalloproteinase inhibitors.
  Biochem. Biophys. Res. Commun. 365(4):650-656, (2008).
  Wagstaff, S.C., Favreau, P., Cheneval, O., Laing, G.D., Wilkinson, M.C., Miller, R.L., Stöcklin, R. and Harrison R.A.
• Evidence of a bactericidal permeability increasing protein in an invertebrate, the Crassostrea gigas Cg-BPI.
  Proc. Natl Acad. Sci. U.S.A. 6;104(45):17759-64, (2007).
  Gonzalez, M., Gueguen, Y., Destoumieux-Garzòn, D., Romestand, B., Fievet, J., Pugnière, M., Roquet, F., Escoubas, J.M., Vandenbulcke, F., Levy, O., Sauné, L., Bulet, P. and Bachère, E.

We could not resist to investigate Atheris snake venom:

• The venom of the snake genus Atheris contains a new class of peptides with clusters of histidine and glycine residues.
  Rapid Commun. Mass Spectrom. 21:406-412, (2007).
  Favreau, P., Cheneval, O., Menin, L., Michalet, S., Gaertner, H., Principaud, F., Thai, R., Ménez, A., Bulet, P. and Stöcklin, R.

Doubtless a key article:

• 'Venomics' or: The venomous systems genome project.
  Editorial. Toxicon 47(3):255-259, (2006).
  Ménez, A., Stöcklin, R. and Mebs, D.

... and there is much more, see our extended list of selected literature.

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