Proteomics for biodefense 2005

 

Biodefense research is generally focused to protect humans and animals against the intentional use of pathogens. It is based on knowledge and understanding gained through genomics and proteomics.

 

Nevertheless, biodefense has also an impact on security for protection against illegal intrusions. This particular application is referred to human authentication.

Some basic terms

Biological warfare

It refers to the military employment of microbial or other biological agents (including bacteria, viruses, and fungi) or toxins (and analogues, whatever their origin or method of production) to produce  death, temporary incapacitation, or permanent harm in humans or to kill or damage animals or plants for a military objective

Biologicaal weapons

They refer to munitions, equipment or other means of delivery, including bombs, aircraft spray tanks and other devices, intended for use in the dissemination (aerosol, spray) of biological agents and toxins for hostile purposes.t

Biological weapons agents

They refer to microbial and other biological agents and toxins, when intended for use in biological weapons. These  are also referred to as select agents, with secondary reference to the disease they cause.

Reference: "Biological Weapons - From the Invention of State-Sponsored Programs to Contemporary Bioterrorism" by Jeanne Guillemin - Columbia University Press, New York (U.S.A.) (2005)

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Protein identification

 

 

  Bullet  Protein separation technologies

  Bullet  Protein expression ("biosignatures", putative protein candidates for specific targets)

  Bullet  Protein structure determination

  Bullet  Protein assembly

  Bullet  Protein network within cells and organisms

 

General applications

  Bullet  ADJUVANTS ( immune system enhancers ) - The antigen'independent enhancer factor (LeF) from human dialysate leukocyte extract (DLE)  is associated with a low-molecular-weight substance (mol. wt. 300-600) with a basic character and it is eluted from chromatographic columns together with a hypoxanthine-like substance. By comparison with a synthetic sample of hypoxanthine, the natural LeF and the synthetic purine derivative were unresolved in our HPLC system; in addition they showed the same UV spectrum (with a maximum at 251 nm at pH 2.7) and identical derivatives. Their sensitivity to total acid hydrolysis and their amino acid analyses appeared to be very similar. LeF was completely resistant to treatment with pronase. The hypoxanthine-like molecule present in the LeF preparation and hypoxanthine were transformed by xanthine oxidase (XOD). The new UV-absorbing peak detected in the RP-HPLC elution profile showed (at pH 2.7) two characteristic maxima in the UV spectrum at 232 (or 231) and 286 nm. The biological activity attributed to LeF was resistant to XOD treatment. By size-exclusion HPLC the enhacer activity showed a molecular weight of ca. 300-600 dalton, in accordance with the values obtained from chromatography on the Sephadex G-25 column, calibrated with synthetic peptides. Nevertheless, these data should be treated with caution. In fact the elution order of small molecules is not always correlated with their respective molecular weights, probably as a consequence (i) of aspecific interactions betweethe solutes and the stationary phase and (ii) of the effect of the mobile phase (with reference in particular to the pH values and salt concentrations) on the tertiary structure of the molecules. By chromatography on a cation exchanger (Dowex 50W-X8, H+ ) and on an anion-exchange resin ( Dowex 1-X2, CH3COO- ), the enhancer factor showed a basic character.  The amino acid analysis of the hydrolysed sample of enhancer factor from RP-HPLC showed a peak of glycine and traces of lysine. We assume glycine to originate from the degradation of the hypoxanthine-like molecule present in the sample. In fact, an equivalent amount of hypoxanthine showed the same result, but in this instance the lysine peak was absent. A different oxypurine analogue, xanthine, was resistant to hydrolysis with 6M hydrochloric acid at 110 C. for 15 hours.The enhancer activity is not due to hypoxanthine itself because (i) the synthetic purine derivative is inactive in the employed bioassays and (ii) the biological activity still remains after treatment of the LeF preparation with xanthine oxidase and it is not attributable to the new UV-absorbing peak detected in RP-HPLC. Consequently LeF is linked to a compound that co-elutes with the hypoxanthine in our chromatographic systems. The biological activity of the LeF does not correspond to that attributed by [Sihna et al. (Bio Technology 6 , 810 (1988)] al to the peptides Tyr-Gly and Tyr-Gly-Gly, isolated from a fraction of human peripheral blood leukocytes. In fact, the di- and tripeptides (which are identical with the amino terminal ends of enkephalins) are eluted later than the enhancer activity in the same chromatographic system; Analysis of in vitro PHA-induced transformation by Tyr-Gly, Tyr-Gly-Gly and the DLE show that the two peptides are not responsible for all the enhancer activity of DLE. Therefore, DLE contains enhancer compound(s) not yet completely identified, acting on cells different from those on which the two enkephalin fragments exert their activity.

  Bullet  BIOLOGICAL MARKERS

  Bullet  BIOMIMETICS - "Biomimetic refers to human-made processes, substances, devices, or systems that imitate nature. The art and science of designing and building biomimetic apparatus is called biomimetics, and is of special interest to researchers in nanotechnology, robotics, artificial intelligence (AI), the medical industry, and the military

    • Machine vision
    • Machine hearing systems
    • Signal amplifiers
    • Navigation systems
    • Data converters
    • Neural networks
    • Nanorobot antibodies
    • Artificial organs
    • Biochip
    • Camouflage (Biological systems might also serve as models for improving materials)

  Bullet  DIAGNOSTICS [devices (biosensors) capable of sensing and rapidly identifying chemical and biological weapons in the ecosystem]

  Bullet  MOLECULAR ELECTRONICS [the use of proteorhodopsin ( http://www.biomedcentral.com/1472-6793/2/5   ) and bacteriorhodopsin  (Bruno's Bacteriorhodopsin Bungalow at  http://www.arches.uga.edu/~bgiri/bcmb8010/ ) : these proteins are able to  convert light into other forms of energy for optical and electronic applications, the use of genetically engineered proteins to makw "computer memories"  ("rugged computer memories"), the development of electronics components able to survive in high-radiation environments; bioluminescence applications for the night-vision instrumentation]

  Bullet  NEW MATERIALS (by the use of specific  enzymes from termophilic bacteria : composite materials)

  Bullet  "SELF-REPLICATING" wound-healing technologies, such as methods for growing new skin, growing blood vessels and regenerating bones

  Bullet  THERAPEUTICS (inhibitors of pathogenic enzymes, drugs to treat shock)

  Bullet  VACCINES

"Biomimetic refers to human-made processes, substances, devices, or systems that imitate nature. The art and science of designing and building biomimetic apparatus is called biomimetics, and is of special interest to researchers in nanotechnology, robotics, artificial intelligence (AI)

  Bullet   DEFENSE PEPTIDES ( Tryptyptophyllins )

<more to be added>

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Resources

 

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The silk production

"Mechanism of silk processing in insects and spiders"  by Hyoung - Joon Jin and David L. Kaplan, Nature 424 , 1057 - 1061 (28 August 2003).

THE ARACHNOLOGY HOME PAGE at http://www.arachnology.be/pages/Silk.html

"Nanotechnology makes way for cyborg soldiers" by Antoine Henry at http://www.thestudentunderground.org/article.php?id=70&issue=47

Applications for the production of new materials (material engineering with desired functional properties).

Potential medical applications:

  • to repair damaged knee ligaments
  • to make artificial bone tissue

Potential non-medical applications:

  • to make ultra-strong clothing (for the cyborg soldier), outdoor equipments

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BIODEFENSE

To identify of the organisms that might be used as agents of  biorerrorism and to know the responses of the human immune system to those organisms.  The bioterrorism's impact on the ecosystem (the food chain, air pollution).  How to prevent the contamination

 

 Bullet     Biosensisng

 Bullet     Real Time Monitoring

 Bullet     Real time detection of microbial contaminants (electrochemiluminescence)

 Bullet     Genome sequensing (species and strain comparison and identification; computational intelligence)

 Bullet     Microarray for biodefense (Chips-N-SNPs)

 Bullet     Signatures for extraterrestrial life (Astrobiology)

 

 

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USEFUL   LINKS

Human Protein Reference Databank at http://www.hprd.org

Swiss - Prot Protein knowledgebase  available at : http://www.expasy.org/sprot/  and  http://www.ebi.ac.uk/sprot/

The Institute for Soldier Nanotechnologies http://web.mit.edu/isn/

Federal Biodefense Research FY2003 conference http://www.infocastinc.com/Biodefense/home.htm

Introduction to biowarfare  http://www.msnbc.com/modules/biowarfare/

National Institute of Allergy and Infectious Diseases http://www.niaid.nih.gov/default.htm

American Association for the Advancement of Science http://www.aaas.org/

Research America http://www.researchamerica.org/

National Institutes of Health http://www.nih.gov/

Department of Health and Human Services http://www.hhs.gov/

Department of Defense http://www.defenselink.mil/

P. Brickley, "Homeland security streamlining," The Scientist, November 19, 2002. http://www.biomedcentral.com/news/20021119/04/

Centers for Disease Control and Prevention http://www.cdc.gov/

Department of Energy  http://www.energy.gov/

Environmental Protection Agency http://www.epa.gov/

DOD's Chemical and Biological Defense Program http://www.acq.osd.mil/cp/index.html

Office of Science and Technology Policy http://www.ostp.gov/

T. Agres, "New view from the Hill," The Scientist , November 11, 2002. http://www.biomedcentral.com/news/20021111/04/

AAAS R&D Budget and Policy Program http://www.aaas.org/spp/rd/

Biodefense research  http://www.niaid.nih.gov/biodefense/research/funding.htm

Inframat Corp. (Farmington, CT, U.S.A.) http://www.inframat.com

Arryx Inc. (Chicago, IL, U.S.A.) http://www.arryx.com

BioTraces, Inc  (Herndon, VA, U.S.A.) at http://www.biotraces.com/index.html

Sciperio Inc  (Stillwater, OK) http://www.sciperio.com 

The Bioweapons and Biodefense Freedom of Information Fund http://www.cbwtransparency.org/

Project BIOSHIELD  http://www.whitehouse.gov/news/releases/2003/02/20030203.html

United States Department of Health and Human Services http://www.hhs.gov

Health Resources and Services Administration http://www.hrsa.gov

Council on Private Sector initiatives (CPSI) http://www.cpsi.ahrq.gov

Viral Defense Foundation: a Manhattan Project for Bioterrorism at http://viraldefense.org

Biological and Chemical Weapons Control at http://www.fas.org/main/content.jsp?formAction=325&projectld=4

FAS - Biosecurity Resource Page at http://fas.org/biosecurity/resource/

ReallyReady at http://www.fas.org/reallyready/index.html  - A project of the Federation of Americam Scientists. ReallyReady.org is devoted to providing comprehensive and correct emergency preparedness information for families, businesses, and individuals with disabilities.

  

 

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REFERENCES

Seeking security: pathogens, open access, and Genome databases (2004) (committee on Genomics Databases for Bioterrorism Threat Agents, National Research Council) at: http://www.nap.edu/catalog/11087.html   Read it Online-Free

Opportunities in Biotechnology for Future Army Applications (2001) Board on Army Science and Technology  http://books.nap.edu/books/0309075556/html/7.html#pageto

Bioweapons Convention  (international security) at http://www.i-sis.org.uk/isisnews/i-sisnews13-10.php

Cartagena Protocol on Biosafety (international security) at http://www.biodiv.org/biosafety/default.aspx

Some Thoughts on Biodefense Research by Jan van Aken and Edward Hammond  http://www.inesap.org/bulletin19/bul19art03.htm

Frontier of military technology is the size of a molecule by Barnaby J. Feder, The New York Times (April 2003)

Mechanism of silk processing in insects and spiders  by Hyoung - Joon Jin and David L. Kaplan, Nature 424 , 1057 - 1061 (28 August 2003)

Terrorism Threat Briefing - Tallahassee, FL, U.S.A. (September 9, 2003

Bioterrorism - Public Health Response to Anthrax Incidents of 2001 - GAO (United States General Accounting Office, Washington, DC 20548, U.S.A.) Report

Opportunities in biotechnology for future Army   Board on Army Science and Technology  (BAST) - The National Academies Press (2001) at http://books.nap.edu/books/0309075556/html/15.html#pagetop

Biodefense at NIAID

Enzymes from termophilic bacteria:

  • Isolation, sequencing and cloning in "E. coli" of a new beta galactosidase archaeobacterial gene by  Cubellis, M.V., Rozzo, C., Montecucchi, P.C. and Rossi, M. on  Gene 94 , 89 - 94 (1990)        Back  

Immunoregulins (enhancers and suppressors):

  • Purification of immunomodulatory molecules from peripheral blood leukocytes by Montecucchi, P.C., Caldarini, R., Sanso', M., Bertolaso, A.M., Rosso di San Secondo, V., Piccolo, G. and Sirchia, G. (1990) on  J. Chromatogr. 512, 139 - 147 (1990)
  • Potentiation of cyclosporin A-induced immunosuppression by a lymphocytic low-molecular-weight peptide by Rosso di San Secondo, V.E.M., Aniasi, A., Piccolo, G., Montecucchi, P.C. and Sirchia, G. (1994) on Transplantation Proceedings 26, 3321 - 3322 (1994)
  • New low-molecular-weight immunoregulins by Montecucchi, P.C. on Protein Science 3, Suppl.1, 138 (1994) 
  • Influence of a DLE-extracted lymphocytic suppressor factor on CSA-induced immunosuppression by Rosso di San Secondo, V.E.M., Aniasi, A., Piccolo, G., Montecucchi, P.C. and Sirchia, G. on Biotherapy 9 , 159 - 162 (1996)      Back        

Earth's anonymous inhabitants by Aparna Sreenivasan at: http://scicom.ucsc.edu/SciNotes/0101/bacteria.html

Bacteria Finally See the Light: Harnessing bacterial rhodopsin to produce energy By Daniel Weinstein on Stanford Technology Brainstorm (Fall 2001) at: http://otl.stanford.edu/about/brainstorm/archives/fall01/rhodop.html

Biological Threat Database -A catalog of genetic information related to the use of viruses as biological weapons has been prepared for the U.S. Army by University of Alabama scientists. "In response to the potential use of viruses as biological weapons, we have established the Viral Biological-threat Bioinformatics Resource (VBBR) that collects, catalogs,annotates, and analyzes genetic information related to potential viral threats," according to a recent report on the initiative. See "Development of a Viral Biological-threat Bioinformatics
Resource" by Elliot J. Lefkowitz, October 2003:
http://www.fas.org/irp/threat/cbw/vbbr2003.pdf

August 2003 report from the National Institute of Allergy and Infectious Diseases (NIAID): http://www.fas.org/irp/threat/cbw/niaid0803.pdf

Biosensors for protection of architectures: " Biodetection Architectures " by Henry Abarbanel et al. - Jason - The Mitra Corp. (Virginia, U.s.A. - February 2003)

THE RECIPE FOR RICIN: Examining the legend ; BIOWAR IS HELL ; THE RICIN INDEX - National Security Notes - February 20, 2004 at:  http://www.globalsecurity.org/org/nsn/nsn-040220.htm

Chemical and Biological Arms Control Program (Federation of American Scientists) at: http://www.fas.org/bwc/index.html [Federation of American Scientists at: http://www.fas.org/ ]

Analyzing Pathogen DNA Sequences by Thomas S. Brettin on Los Alamos Science N. 28 (2003)

Reducing the Biological Threat: Detection, characterization and response by Paul J. Jackson and Jill Trewhella on Los Alamos Science N. 28 (2003)

DOD DIRECTIVE ON SAFEGUARDING BIOLOGICAL AGENTS - The Department of Defense last month issued a new directive on security for particularly hazardous biological agents and toxins.

DOD RELEASES STUDY ON ANTHRAX LESSONS LEARNED : " Lessons from the Anthrax Attacks: Implications for U.S. Bioterrorism Preparedness ". The report, authored by David Heyman of the Center for
Strategic and International Studies, is based on a daylong forum convened by CSIS under contract to the Defense Threat Reduction Agency (DTRA) in December 2001.

Biotechnology: Impact on Biological Warfare and Biodefense by James B. Petro, Theodore R. Plasse and Jack A. McNulty on Biosecurity and Bioterrorism: Biodefense strategy, Practice, and Science 1 (3) 161 - 168 (2003)

Biodefense at the Trade Resource Center

Bioterror at The Naval Postgraduate School (NPS)   http://library.nps.navy.mil/home/terrorism.htm

Building a better biosensor by Mike May on The Scientist 18 (10), 36 - 38 (2004) - "A universal biosensor applicable to all bioagents would be the ultimate goal".

Assessing the Agroterror Threat- Report analyzes potential US targets by Steve Nash on The Scientist 18 (9), 50-51 (2004). It should be useful to have "a new "sniffer" sensor technology that continuously samples the air around livestock or food facilities".

Project Bioshield Act of 2004.  "Cracks in the armor" by Candace Stuart, SmallTime 4 (5) , 24 - 28 (2004)

"Biological Weapons - From the Invention of State-Sponsored Programs to Contemporary Bioterrorism" by Jeanne Guillemin - Columbia University Press, New York (U.S.A.) (2005)

 

 

Some useful links

Disclaimer for External Links

Amersham Biosciences - Chromatography

http://www.chromatography.amershambiosciences.com

BiologyBrowser.org

http://www.biologybrowser.org

Biomedical Acronym Database

http://invention.swmed.edu/argh

BioScreening.com: Drug Discovery Portal

http://www.bioscreening.com

Center for biological sequence analysis

http://www.cbs.dtu.dk/index.shtml

CKAAPs Database (protein sequence and structure (CKAAPs is an acronym from Conserved Key AminoAcid Positions)

http://ckaaps.sdsc.edu/perl/browser.pl

Genome.gov

http://www.genome.gov

iHOP - Information Hyperlinked over Proteins

http://www.pdg.cnb.uam.es/UniPub/iHOP

Human serum proteome

http://bpp.nci.nih.gov

Merops: The peptidase database

http://merops.sanger.ac.uk

Nuclear protein database

http://npd.mrc.ac.uk

PCR Links.com - The web guide of polymerase chain reaction technique

http://www.pcrlinks.com

Protein lounge

http://www.proteinlounge.com/default.asp

Proteomics at the NCI

http://web.ncifcrf.gov/rtp/prot/site/default_flash.asp

Theoretical and computational biophysics group

http://www.ks.uiuc.edu/Development/biosftdb

Swiss EMBnet Node Server

http://www.ch.embnet.org/index.html

WorldQ.com: search for knowlwdge

www.wordiq.com