In this section you will learn how to get started with the Biology Workbench; namely, opening an account, logging into your account, and creating a session (i.e. folder) to store your data.

Opening An Account
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Go to the Biology Workbench homepage in Workbench panel. Click on the link that says, "Registration". If you already have an account, go ahead and log into the program. If not, you need to open an account first.  It is free and it is available immediately. Once your account is created, you will be taken to another website Click on the link that reads Biology Workbench to go to the main page.

Starting a New Session
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There are a few different sets of tools supplied by the Workbench. They are Session Tools, Protein Tools, Nucleic Tools, Alignment Tools and Structure Tools (Alpha). To maintain some organization in your research, you should create a new session for every new topic you research.
1. From the window highlight the line that reads Start New Session and click Run, You will be taken to another window
2. Type the name of the new session, for example, PRIONS, in the space provided and then click the Start New Session button You will be taken to another window.

Once set up with your own account and new session you can really begin. In this section you will learn how to search databases for protein sequences. Finding the wild type prion protein sequence is a great way to get started.

Importing Sequences from Protein Databases
1. Clicking on Protein Tools will take you to the Protein Tools homepage. Notice the scrollable menu at the top of the page . . . this box contains a variety of tools, some of which you will now explore.


2. Now you are going to search the databases to find the wild type prion protein sequence. Highlight Ndjinn-Multiple Database Search. Then click on Run.


3. The next screen lists the different databases that you can search. In the search box at the top of the page type: "Prion". This tells the search engine what to look for. Also, notice the drop-down menu to the right of the input box. This simply allows you to decide how many sequences you want to display. For this exercise, you want to see all of the sequences that are found so select Show All Hits.


4. Scroll down the page. Below you will see a list of several different databases; all containing a variety of sequence information. There are two groupings of databanks that are separated from one another: the first contains sequences from many different organisms (e.g. GBBCT - - contains a large number of sequences from all of the different bacterial genomes that have been sequenced ), whereas the second group contains the entire genome sequences of specific organisms (e.g. Mthe contains the entire genome of Methanobacterium thermoautotrophicum).

Since you are focusing on humans click on the box that is next to the GBPRI database. This is the GenBank: Primates Sequences database. This databank contains protein sequences that are specific to primates only, and thus humans. Place a checkmark in the box next to this database. Then scroll back up to the top and click on Search. A screen containing the search results will appear.



5. Highlight (click on) the sequence: gbpri: 190467 ¡V human prion protein (prp) mrna, complete cds. Click on Import Sequence(s). This action will send you and the gbpri: 190467 sequence to the Protein Tools homepage.



As you can see there are a large number sequences from which to chose. How did we decide which sequence was the best? The desired sequence was determined by using the Show Record(s) tool. Clicking on Show Record(s) brings up a new window (a separate window if you are using Netscape) that contains information about the sequence(s) that you selected (i.e. from what organism it was derived).

6. We already have found the wildtype prion sequence, let's see what it looks like. Check the box next to the wildtype 190467_190468 sequence, then scroll down the menu and highlight "View Protein Sequence(s)". Click on the "Run" button.



7. A window containing the sequence of the wildtype prion protein will appear. The letters you see each stand for an amino acid. If you take a close look, you will see a short octapeptide sequence (or eight amino acids in a row) that is repeated 5 times. See if you can find the repeated sequence. If you have some trouble, look at the figure below (the first repetitive sequence is highlighted).



8. Starting at this first octapeptide sequence, follow the sequence until you have found all five octapeptide sequence repeats. Each repeat with the exception of the last repeat has the sequence GGGWGQPH (the last of the five repeats which is highlighted below has the sequence GGGWGQGG).



9. Now that we have found the wildtype prion protein sequence, let's see how it differs from a mutant prion sequence that causes Creutzfeldt-Jakob Disease in humans.