Cell Cycle, Cancer, and the Biology Student Workbench

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Cell Cycle, Cancer, and the Biology Student
Workbench

• An intro to what BSW can do
• 2002
• Steve Moore Kathy Gabric

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p53

• p53 is a tumor suppressor gene.
• It turns on other genes that inhibit the cell
  cycle.
• If p53 is mutated, the mutant form results in a
  protein that cannot perform its function. Its
  disruption is associated with approximately 50 to
  55 percent of human cancers
• As a result, the cell cycle has no brakes to
  slow it down, and it proceeds at a reckless speed.

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p53

• p53 can tell the cell to commit suicide.
• This is called apoptosis or programmed cell
  death.
• If p53 is mutated, the cell looses its ability to
  have cancer cells kill themselves.
• A mutated p53 can be inherited from one
  generation to the next. The mutation may cause
  cancer, or may make it more susceptible to tumor
  causing viruses attaching and inactivating the
  gene.

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p53 Keeping Cancer in Check

• The p53 tumor suppressor and its surrounding
  molecules are now the focus of thousands of
  studies in laboratories around the world.
• These studies may one day lead to new treatments
  for the most frequent and life-threatening of
  cancers.

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This is what p53 looks like.
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How can a scientist studying p53 find its amino
acid sequence?
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BSW is a tool to search databases for protein and
DNA sequences.
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Lets Begin!

• Go to

Biology Student Workbench
Just click on the words above to begin. We
suggest you keep this window open and have BSW
open in another.
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Biology Student Workbench

• Click on
• Student Interface to the Biology Workbench (SIB)
  You may have to do this through several pages.
• Type in username and password and then submit
• PS. You will have to register first if you have
  not yet done so. Its Free!

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Create a New Session

• You have numerous options that are self
  explanatory.
• BSW will save all of your work sessions for you.
• Today, we will create a new session and call it
  cancer.

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Choose Protein Tools

• The tools available to you and a description of
  their use is provided for you.
• First use
• Multiple database search for protein sequences
• Type in p53 and select the GenBank Primate
  sequence.
• Click Ndjinn to activate the tool.

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Hard Part!

• Look for Human p53 (TP53) gene, complete cds.
  (Complete DNA Sequence)
• Lots of other partial sequences, DNA fragments,
  exons and introns, and other animal DNA are
  given.
• Place a check next to it and import the sequence.
• The sequence will be saved at the bottom of the
  page.

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Amino Acid Sequences

• Compare a Protein sequence to a protein sequence
  database
• Choose GenBank Primate Sequences
• Check your imported sequence
• Activate the tool by clicking on BLASTP

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Find a similar protein

• The higher the score, the more closely related
  the proteins will be.
• In looking for a mutation, they should be very
  similar with only a few changes.
• For this activity choose tumor protein p53
  (Li-Fraumeni syndrome)...
• Check it and import the sequence.

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Compare the Sequences

• Align multiple protein sequences with each other.
• Select the 2 proteins you have saved.
• Activate the tool by clicking on CLUSTALW

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Compare the Sequences

• The letters in blue mean that the amino acids are
  highly conserved. In real people terms, it means
  they are the same.
• Notice the change from proline in the normal p53
  gene to alanine in the Li Fraumeni p53 gene.
• This means that the DNA was mutated and as a
  result it coded for the wrong amino acid.
• Import this alignment to save it.

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So whats the big problem with 1 wrong amino acid?

• Really how different are proline and alanine
  anyway?

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Proline vs. Alanine
Proline
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I still dont see what the big problem is!

• What does this little switch actually do to the
  person?

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Li Fraumeni Syndrome

• Li-Fraumeni syndrome is a cancer prone
  disease. Prognosis most common cancer in
  Li-Fraumeni children are soft tissues sarcoma
  before the age of 5 yrs and osteosarcoma
  afterwards, and breast cancer in young adults
  other frequent cancers brain tumors, leukemias,
  adrenocortical carcinoma 1/3 of patients have
  developed more than one primary cancer, which is
  quite characteristic of Li- Fraumeni syndrome.
  Cancers in this disease, as in other cancer-prone
  diseases, often occur early in life 50 of
  patients aged 30 yrs have had a cancer and 90
  have had cancer by age 60 yrs.

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So what about the DNA that resulted in this?
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Choose Nucleic Tools

• The tools available to you and a description of
  their use is provided for you.
• First use
• Multiple database search for nucleic sequences
• Type in p53 and select the GenBank Primate
  sequence.
• Click Ndjinn to activate the tool.

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Hard Part!

• Look for Human p53 (TP53) gene, complete cds.
  (Complete DNA Sequence)
• Lots of other partial sequences, DNA fragments,
  exons and introns, and other animal dna are
  given.
• Place a check next to it and import the sequence.
• The sequence will be saved at the bottom of the
  page.

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Find a similar, but mutated sequence.

• Do Ndjinn search for Li-Fraumeni Syndrome
• An odd quirk is that you must enter it as
• li-fraumeni exactly. Choose the GenBank Primate
  sequences click on Ndjinn
• Import this nucleic sequence.
• Select both sequences and align them by clicking
  on ClustalW
• Compare the sequences.

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Whats Up?

• How does this compare to what we saw in the
  protein sequence?
• How can we explain the differences?

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BSW is a tool to analyze databases for protein
and DNA sequences.

• This tool can be used for research into proteins
  and the important jobs they do.
• Or to find out why an alteration in the protein
  results in a disease state.
• The problem may ultimately lie in the DNA, and
  BSW can be used to determine its sequences to.

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How could you use Biology Student Workbench?

• Any ideas for projects youd like to try?