SMART TEAM
Students Modeling A Research Topic: The Journey Explained
What is SMART Team?
Definition: science program
where high school students learn
about a specific protein and
construct a three-dimensional
model of that protein.
Team
Anna Grim
Bryan Lampkin
Dua Her
Rachel Babiarz
The University’s Center for
BioMolecular Modeling is
the center for SMART
Team.
Milwaukee School Of Engineering
Funding: NIH National Center for
Research Resources, Department of
Education for Educational Sciences
and Howard Hughes Medical Institute.
Purpose
Focus: to tell the
“molecular story” of NS1
protein and influenza
infections. In addition,
modeling the NS1 protein.
Modeling Tool: Rasmol
Rasmol
Definition: computer modeling program.
Models are created by using commands to
highlight specific parts of the protein.
Proteins were downloaded from a national data bank.
Part 1
Virus Background Information&
The NS1 Protein
“So What?”
–Learning how viruses/influenzas invade (such as H5N1 and H1N1)
– Understanding how our immune system battles against the flu
– Increased knowledge of NS1 can help avoid future viruses
–Relates to stronger and nastier influenzas (such as swine flu)
Virology
The branch of medicine that
focuses on the study of
viruses
Micro-Anatomy of Virus
-Nucleic acid enclosed in a protein shell.
-Approximately 15-20 nanometers in diameter.
-May have DNA or RNA that is double-stranded or single-stranded .
-Genetic material is covered by a protein coat.
http://www.google.com/images?q=anatomy+of%20a%20virus&um=1&hl=en&client=
How Does a Virus Invade?
1. Virus enters body.
2. Virus’s Antigen binds to cell through hemagglutinin.
3. Virus enters the cell through endocytosis.
4. A clathrin-coated vesicle is formed around the virus.
http://www.invivogen.com/images/RLR_pathway.jpg
How Does a Virus Invade?
6. Virus’ RNA passes through the nucleus and is replicated.-Lysogenic Cycle-Lytic Cycle
7. The replicated viruses leave the cell.
Fact: One virus enters the cell
and results in the replication
of millions of viruses that
leave the cell.
5. Once inside the cell, the vesicle breaks apart.
– NS1 protein (non-
structural protein)
– Found in a virus
– Encoded within an
influenza virus
The NS1 Protein
http://web5.cns.utexas.edu/news/wp-content/uploads/2009/12/NS1A-PNAS_cover4.jpg
Taking a Closer Look
• The NS1 protein is a gene segment located in the inside of a virus
• Influenza A, B, and C viruses contain the NS1 protein
• Viruses with NS1 protein are H5N1 (bird flu) and H1N1 (swine flu)
NS1’s Role
• Binds RNA messengers of host cell from activation
• Attacks TRIM-25 protein – TRIM-25 assists RIG-1
protein– RIG-1 sends out alarm
signals throughout cell
• Slows down pre-mRNA production of a cell
http://focus.hms.harvard.edu/2007/051807/images/RIG-I-TRIM25.gif
A Sign of Hope?– An Antiviral Target against Influenza?
• NS1 binds to the CPSF30 human protein
• CPSF30 protects our cells from infections
• Within the binding site, zinc fingers (F2,F3) from the CPSF30 protein cuts down the virus’s ability to duplicate by blocking the binding between CPSF30 and the NS1 protein
• This binding site can suggest a potential antiviral target against the influenza virus
http://web5.cns.utexas.edu/news/wp-content/uploads/2009/12/NS1A-PNAS_cover4.jpg
Protein Modeling
NS1 Protein Before
NS1 Protein After
NS1 Protein
GuideYellow: Active Site
Green: 7 Beta Sheets
Blue: 3 Alpha Helices
Orange: Hydrogen Bonds
Immunology
The branch of medicine concerned with the
ability of an organism to resist a infection by
the action of antibodies.
Immunity
Innate Immunity: defends the host
from infection by an immediate
nonspecific respond to pathogens.
Adaptive Immunity: antigen-specific
immune response and includes a
"memory" that makes future
responses against a specific antigen.
Acquired Immunity: acquired by the vaccination of the transfer of antibody
.
Innate vs. Adaptive Immunity
Immunology
T-cells: identify, directly attack and
destroy infectious agents.
Interferons: proteins made and
released by lymphocytes in
response to the presence of
pathogens - such as viruses,
bacteria, or parasites.
RIG-1: required for the production
of interferons in response to RNA
viruses.
Immunology
Macrophages: molecules that
engulf antigens and other necrotic
tissue.
Cytokines: signaling molecules that are used in cellular communication.
Tumor Necrosis Factor: cytokine involved in a systemic inflammation and is a member of a group of cytokines that stimulate the acute phase reaction.
http://www.itb.cnr.it/flex/images/D.0ce220a1911164afd50b/boraschi_1.jpg
Definition: method of determining the
arrangement of atoms within a crystal, in
which a beam of X-ray strikes a crystal
and diffracts into many specific directions.
In 1962 they were awarded the Nobel Prize in Chemistry.
Began in the 1950s when Max Perutz and Sir John Cowdery Kendrew used it to
study the structure of sperm whale myoglobin. http://ysm.research.yale.edu/images/78.4/articles-structures-crystallography.jpg
Crystallography
Part 2
The Interferon (IFN) &
relation with NS1 Protein
Interferon• Detects and fights off infections invading our body
• Classified as a Cytokines– Cytokines are from the immune system– Purpose is to warn the cells of invasions
• Role of Interferon:– Triggers other immunity cells to activate – Builds up other uninfected cells’ resistant towards the new
infections– Forms interferon-stimulated genes (ISGs) to fight off
viruses
Types of Interferons
• Type I IFN (alpha and beta)
–Produces cells resistant against viral infections–Produced from cells in the body
• Type II IFN (gamma)
–Control how the immune system functions–Produced from T lymphocytes and natural killer cells
Connection with NS1
• Interferons decrease the virus’s ability to spread
•Unfortunately, not all viruses are affected by interferons
•Example: H1N1 influenza virus is encoded with a Non-Structural Protein 1 (NS1)
•NS1 resists the presence of interferons…not good
Conclusions• Viruses that contain NS1 protein are harder to get rid of
• Our immune systems are not familiar with new viruses
• Immune systems takes longer to destroy viruses with NS1 protein
• Knowing about NS1 now can aware us of future nastier viruses
• Studies are being done to shut down NS1 protein receptor
Acknowledgements
–Dr. Shannon Colton (SMART team coordinator)
–MSOE - Center of Biomolecular modeling
–SMART team program
–Rasmol program
–Mr. Heeren (assisting DCE SMART team)
Bibliography
• Featured Website: WWW.GOOGLESCHOLAR.COM
•http://www.onmilwaukee.com/images/articles/ho/holidaycarepackage/holidaycarepackage_fullsize_story1.jpg
• http://viromag.files.wordpress.com/2009/02/influenza-virus-diagram.jpg• http://www.invivogen.com/images/RLR_pathway.jpg
•http://science.nationalgeographic.com/staticfiles/NGS/Shared/StaticFiles/Science/Images/Content/flu-virus-e06074-xl.jpg
• http://web5.cns.utexas.edu/news/wp-content/uploads/2009/12/NS1A-PNAS_cover4.jpg• http://focus.hms.harvard.edu/2007/051807/images/RIG-I-TRIM25.gif
• http://ysm.research.yale.edu/images/78.4/articles-structures-crystallography.jpg• http://pathmicro.med.sc.edu/book/immunol-sta.htm
• http://pathmicro.med.sc.edu/ghaffar/innate.htm• http://www.geneontology.org/images/diag-immunology-sm.png
• http://www.ncdnaday.org/immunology.jpg• http://www.cbi.wur.nl/NR/rdonlyres/B299B497-3031-48C6-BFB8-B6DCDCCC93D4/94540/
• http://www.vet.cornell.edu/oge/immunology/pix/Clark1.jpg