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Title

Interactive session for PhD students - Swiss Microbial safety Meeting 2013

Dates

January 14 & 15, 2013

Responsable de l'activité

Stefan Kunz

Organizer(s)

Prof. Stefan Kunz UNIL/CHUV

Prof. Pascal Meylan, UNIL/CHUV

Speakers
see Program
Description
Interactive session for Ph.D students at the Swiss Microbial Safety Meeting 2013
Description of the activity

This activity consists of an interactive session for Ph.D students at the Swiss Microbial Safety Meeting 2013 on January 14 2013. The goal of this interactive session is to sensitize the awareness of our students for biological risks they may encounter during their research activity in microbiology. This will be achieved in an exercise in which students will prepare and present a microbiology research project under the aspect of biological risk assessment and biosafety classification in front of international and national experts in biosafety.

The activity will include a maximum of 10 groups of two Ph.D. students each. The students will receive the description of a specific research project in microbiology together with a research article and a more general review on the topic from the resident experts (Meylan, Folletti, and Kunz) at least 1 month before the meeting. Topics will include the study and the generation of novel pathogenic microbes that are a potential threat for humans, agriculture, and/or the environment. The students will prepare a presentation of their project with particular consideration of biosafety risk assessment. As a result of their work, the students have to define the appropriate biosafety category of the work that they propose.

 At the meeting 1 hour will be allocated for the final work on the presentation (8 minutes of presentation + 4 minutes of discussion) with support from the experts. In the following interactive session, the students will present their projects to the experts and the other participants of the meeting in a 2 hour interactive session.  After the presentation, the students will meet with the experts in a round-table discussion of at least 1 hour to evaluate their presentations and receive feedback on their biosafety risk assessment.  

 
Projects to evaluate from a biosafety standpoint

Project 1: Creation of a “killer poxvirus”   

Poxviruses belong to the most pathogenic viruses with smallpox being the worst disease that ever affected mankind, killing more people than all other diseases, natural disasters and wars combined. A major reason for the virulence of poxviruses is their ability to suppress host immunity. In 2001, a recombinant mousepox (Ectromelia) virus has been reported that expressed the anti-inflammatory cytokine IL-4 and showed markedly enhanced virulence in animal experiments. The generation of this “killer poxvirus” raised significant concerns about biosafety of this type of recombinant poxviruses.

Article describing the study:

Jackson RJ et L, Expression of mouse interleukin-4 by a recombinant ectromelia virus suppresses cytolytic lymphocyte responses and overcomes genetic resistance to mousepox. J Virol. 2001 Feb;75(3):1205-10.

For this project, the following questions should be addressed:

1. What makes IL-4 expressing Ectromelia virus vectors “killer poxviruses”?

2. What are the biosafety risk concerns for studies with this virus?

3. What biosafety precautions and biosafety classification are needed for this type of study?

4. Should this type of studies be performed at all?

Recommended articles for background information:

Müllbacher A, Lobigs M. Creation of killer poxvirus could have been predicted. J Virol. 2001 Sep;75(18):8353-5

Stanford, M and McFadden, G. The ‘supervirus’? Lessons from IL-4-expressing poxviruses. Trends in Immunology Vol.26 No.6 June 2005

 

Project 2: A highly pathogenic emerging virus: Sin Nombre Hantavirus

Hantaviruses are rodent-borne viruses that have been emerging over the past decades and can be associated with severe human disease. The hantaviruses Sin Nombre virus (SNV) and Andes Virus (ANDV) have emerged in North- and South America as causative agents of a severe human respiratory disease, hantavirus pulmonary syndrome (HPS). In America the fatality rate of infection with ADNV and SNV is close to 30% and human transmission has been shown making these viruses a particular concern for public health. There is currently no licensed vaccine against hantaviruses and therapeutic options are restricted making hantaviruses some of the most dangerous pathogens. The study in question investigates the interaction of SNV with the host cell.

Article describing the study:

Hussein IT, Cheng E, Ganaie SS, Werle MJ, Sheema S, Haque A, Mir MA. Autophagic clearance of sin nombre hantavirus glycoprotein gn promotes virus replication in cells. J Virol. 2012 Jul;86(14):7520-9. Epub 2012 May 2.

For this project, the following questions should be addressed:

1. What are the biosafety risk concerns for studies with this virus, in particular regarding transmission?

2. What biosafety precautions and biosafety classification are needed for this type of study according to federal rules and regulations?

3. What additional safety precautions would you enforce in your laboratory when performing this study?

Recommended article for background information:

Jonsson, C. B., L. T. Figueiredo, and O. Vapalahti. 2010. A global perspective on hantavirus ecology, epidemiology, and disease. Clin Microbiol Rev 23:412-41.

 

Project 3: Ebola virus

The filovirus Ebola virus belongs to the most virulent pathogens with a case mortality of over 90% for some strains and isolates. In humans Ebola virus can cause a severe and often hemorrhagic shock syndrome. There is no vaccine against Ebola virus and current therapeutic options are limited to supportive care. The present study investigates cellular factors that are involved in Ebola virus infection in human cells.  

Article describing the study:

Miller ME, Adhikary S, Kolokoltsov AA, Davey RA. Ebolavirus requires Acid sphingomyelinase activity and plasma membrane sphingomyelin for infection. J Virol. 2012 Jul;86(14):7473-83. Epub 2012 May 9.

For this project, the following questions should be addressed:

1. What makes Ebola virus such a virulent pathogen?

2. What are the biosafety risk concerns for studies with this virus?

3. What biosafety precautions and biosafety classification are needed for this type of study?

Recommended article for background information:

Feldmann H and Geisbert TW. Ebola hemorrhagic fever. Lancet 2011  377: 849

 

Project 4: Botulinum toxin

Botulinum toxin is one of the most toxic biological agents at the origin of botulism a life-threatening illness in humans and animals. Botulinum toxin can be used in a wide breadth of settings ranging from the most positive as clinical treatment to the most negative as biological weapons or bioterrorism. The present study investigates the antigenic potential of different protein fragments to develop a more effective vaccine.

Article describing the study:

Stahl C, Unger L, Mazuet C, Popoff M, Straub R, Frey J. Immune response of horses to vaccination with the recombinant Hc domain of botulinum neurotoxin types C and D. Vaccine. 2009 Sep 18;27(41):5661-6. Epub 2009 Jul 29.

For this project, the following questions should be addressed:

1. What makes Botulinum neurotoxin such a dangerous protein?

2. What are the biosafety risk concerns for studies with this pathogen?

3. What biosafety precautions and biosafety classification are needed for this type of study?

Recommended article for background information:

Karalewitz AP, Barbieri JT. Vaccines against botulism. Curr Opin Microbiol. 2012 Jun;15(3):317-24. Epub 2012 Jun 12.

 

Project 5: Staphylococcus aureus

The Staphylococcus aureus is frequently found in the human respiratory tract and on the skin. Not always pathogenic, it is a major human pathogen associated with a wide spectrum of diseases (skin infections, respiratory disease and food poisoning). Methicillin-resistant strains of S. aureus (MRSA) are a global cause of hospital-associated infections. The present study analyzes the importance of the carotinoid pigment to S aureus enhanced oxidant and neutrophil resistance.

Article describing the study:

Liu GY, Essex A, Buchanan JT, Datta V, Hoffman HM, Bastian JF, Fierer J, Nizet V. Staphylococcus aureus golden pigment impairs neutrophil killing and promotes virulence through its antioxidant activity. J Exp Med. 2005 Jul 18;202(2):209-15. Epub 2005 Jul 11.

For this project, the following questions should be addressed:

1. What makes S. aureus such a virulent pathogen?

2. What are the biosafety risk concerns for studies with this pathogen?

3. What biosafety precautions and biosafety classification are needed for this type of study?

Recommended article for background information:

Fitzgerald-Hughes D, Devocelle M, Humphreys H. Beyond conventional antibiotics for the future treatment of methicillin-resistant Staphylococcus aureus infections: two novel alternatives. FEMS Immunol Med Microbiol. 2012 Aug;65(3):399-412. doi: 10.1111/j.1574-695X.2012.00954.x. Epub 2012 Apr 4.

 

Project 6: H5N1

The H5N1 is a subtype of the influenza A virus which can cause illness in humans and other animal species. The present study describe how to create H5N1 influenza A virus that can be transmitted via respiratory route between ferrets and rise several questions and controversies around publishing potential dual-use data.

Article describing the study:

Herfst S, Schrauwen EJ, Linster M, Chutinimitkul S, de Wit E, Munster VJ, Sorrell EM, Bestebroer TM, Burke DF, Smith DJ, Rimmelzwaan GF, Osterhaus AD, Fouchier RA. Airborne transmission of influenza A/H5N1 virus between ferrets. Science. 2012 Jun 22;336(6088):1534-41.

File Suppl. Mat.

For this project, the following questions should be addressed:

1. What makes H5N1 such a virulent pathogen?

2. What are the biosafety risk concerns for studies with this pathogen?

3. What biosafety precautions and biosafety classification are needed for this type of study?

Recommended article for background information:

Watanabe Y, Ibrahim MS, Suzuki Y, Ikuta K. The changing nature of avian influenza A virus (H5N1). Trends Microbiol. 2012 Jan;20(1):11-20. Epub 2011 Dec 5. Review.

 

 

Project 7: Schmallenberg Virus

During the second semester of 2011, a newly described bunyavirus has spread throughout Europe and infecting ruminants, particularly sheeps, causing non specific clinical signs and malformations in fetuses from infected mothers.  There is an obvious research and diagnostic need to deal with this virus of potential major economic significance

Articles describing the problem:

Virus de Schmallenberg, Office Vétérinaire Fédéral, available in the three national languages

For this project, the following questions should be addressed:

1. Is this virus a medical (human pathogen) concern?

2. What are the biosafety risk concerns for studies with this virus?

3. What biosafety precautions and biosafety classification are needed for this type of study?

Recommended article for background information:

SCIENTIFIC REPORT OF EFSA "Schmallenberg" virus: Analysis of the Epidemiological Data and Assessment of Impact, European Food Safety Authority (EFSA), Parma, Italy, EFSA Journal 2012;10(6):2768, www.efsa.europa.eu/en/efsajournal/doc/2768.pdf

Fleming  DO.  Risk Assessment of Biological Hazards (Chapter 5, p 81-91), in Biological Safety Principles and Practices, 4th ed.  Fleming DO and Hunt DL, eds. ASM Press, 2006, Washington DC.

 

 

Project 8: Influenza A chimeric glycoproteins

Influenza A viruses can cause influenza of varying severity, from relatively mild cases as in seasonal epidemics, to more severe pandemic  influenza (such as during the 1918 spanish flu caused then by H1N1, characterized by about 2% mortality), to very severe zoonotic flu as exemplified by the H5N1 avian flu since 2003, with a more than 50% mortality rate in cases.  Various viral genes have been implicated in determining this pathogenic power.  The present study describes chimeric constructs from different influenza hemagglutinins, and the production of functional viruses containing these chimeric glycoproteins

Article describing the study:

Hai R, Krammer F, Tan GS, Pica N, Eggink D, Maamary J, Margine I, Albrecht RA, Palese P. Influenza viruses expressing chimeric hemagglutinins: globular head and stalk domains derived from different subtypes. J Virol. 2012 May;86(10):5774-81. doi: 10.1128/JVI.00137-12. Epub 2012 Mar 7.

Influenza viruses expressing chimeric hemagglutinins: globular head and stalk domains derived from different subtypes.

For this project, the following questions should be addressed:

1. What is the role of influenza hemagglutinin in determining the virus pathogenic power (virulence)?

2. What are the biosafety risk concerns for studies with this virus?

3. What biosafety precautions and biosafety classification are needed for this type of study?

Recommended article for background information:

Satoshi Fukuyama, Yoshihiro Kawaoka. The pathogenesis of influenza virus infections: the contributions of virus and host factors.  Current Opinion in Immunology. Volume 23, Issue 4, August 2011, Pages 481–486

 

Project 9: Recombination in Herpesviruses

Live attenuated Herpesvirus vaccines are widely used  inhuman and veterinary medicine.  When co-infecting host cells, they can recombine with closely related viruses.  The present study describes the testing of a recombinant avian herpesvirus expressing highly pathogenic avian influenza hemagglutinin

Article describing the study:

S.P. Pavlova, J. Veits, G.M. Keil, T.C. Mettenleiter, W. Fuchs. Protection of chickens against H5N1 highly pathogenic avian influenza virus infection by live vaccination with infectious laryngotracheitis virus recombinants expressing H5 hemagglutinin and N1 neuraminidase. Vaccine, 27 (5) (2009), pp. 773–785

For this project, the following questions should be addressed:

1. What is the pathogenicity of highly pathogenic avian influenza in the frame of the recombinant vaccine

2. What are the biosafety risk concerns for studies with this virus?

3. What biosafety precautions and biosafety classification are needed for this type of study?

4.  What could go wrong in large scale application of this vaccine

Recommended article for background information:

Thiry E, Meurens F, Muylkens B, McVoy M, Gogev S, Thiry J, Vanderplasschen A, Epstein A, Keil G, Schynts F. Recombination in alphaherpesviruses.  Rev Med Virol. 2005 Mar-Apr;15(2):89-103

Lee SW, Markham PF, Coppo MJ, Legione AR, Markham JF, Noormohammadi AH, Browning GF, Ficorilli N, Hartley CA, Devlin JM. Attenuated vaccines can recombine to form virulent field viruses. Science. 2012 Jul 13;337(6091):188.

 

Project 10: Lentiviral vector expressing a growth factor

Recombinant viruses expressing genes of interest are extremely widely used tools in biology and medicine (gene therapy vectors).  The evaluation of the risks of such viruses is relatively complex.  In particular, when the transduced gene encodes a gene product able to sustain cell and/or tumor growth, there is a concern regarding cell transformation and tumorigenesis

Article describing the study:

Sun XZ, Liu GH, Wang ZQ, Zheng FF, Bian J, Huang YP, Gao Y, Zhang YD, Deng CH. Chin Over-expression of VEGF165 in the adipose tissue-derived stem cells via the lentiviral vector. Med J (Engl). 2011 Oct;124(19):3093-7.

 

For this project, the following questions should be addressed:

1. What could be the adverse effect of VEGF165 over-expression

2. What are the biosafety risk concerns for studies with this virus vector?

3. What biosafety precautions and biosafety classification are needed for this type of study?

 

Recommended article for background information:

Recommendation of the SECB on the risk assessment of activities using oncogenic and cytokine-encoding sequences.  Swiss Expert Committee for Biosafety SECB, c/o Federal Office for the Environment FOEN, 3003 Berne, Phone +41 (31) 323 03 55, Fax +41 (31) 323 03 69,. www.efbs.admin.ch / [email protected]

 

Rapisarda A, Melillo G. Role of the VEGF/VEGFR axis in cancer biology and therapy. Adv Cancer Res. 2012;114:237-67

 

Location

EPFL

Credits

1

Information
Location: EPFL campus, auditorium SV1717 (Building SV, School of biological sciences)
More information and Program
 
If you are interested in this course, please:
  1. Register online to attend the Swiss Microbial Safety Meeting 2013 (link)
  2. Register for the CUSO activity on line
 
Important: the CHF 50.00 Conference fee will be reimbursed by the CUSO doctoral program via the CUSO reimbursement form.
Places

20

Deadline for registration 15.12.2012
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