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Modified Protocol for Western Blotting (Page 123)--Western Blotting Center

 

D. Running the gel

  1. After briefly spinning the samples, load into the wells.
  2. Be sure to use protein markers.
  3. Run with constant current or voltage. (We usually run the gel with 100v constant voltage first, and then adjust according to the shift of bands.)
  4. Usual running time is about 1.5-2.5 hrs.

E. Using precast gels (Ready Gels):

  1. Assemble gel in gel rig.
  2. Prepare protein samples.
  3. Use a standard protein marker.
  4. Run with power supply at 100v first and adjust according to the shift of bands.

F. Preparation of membrane

  1. Cut a piece of polyvinylidene difluoride (PVDF) membrane.
  2. Wet for about 30 min in methanol on a rocker at room temp.
  3. Remove methanol and add 1x Blotting buffer until ready to use.

Note: Just wet it with cooled blotting buffer for 30 minutes, if you select nitrocellulose.

G. Membrane transfer

  1. Assemble "sandwich" using a transfer.
  2. Prewet the sponges, filter papers (slightly bigger than gel) in 1x Blotting buffer.
         Sponge - filter paper - gel - membrane - filter paper - sponge
  3. Transfer for 1 hr at 1 amp constant current (or 100 voltage constant voltage) at 4°C on a stir plate.
         Bigger proteins might take longer to transfer.
    Note: the time or current (or voltage) is different from lab to lab. You can change them according to the apparatus you are using and your experience at the lab.
  4. When finished, immerse membrane in Blocking buffer and block at 4ºC overnight, or one hour at room temperature.

Note: In order to get a good blot, we suggest to make the transferring buffer freshly every time you do Western blotting.

 

H. Antibodies and detection

  1. Incubate with primary antibody diluted in Blocking buffer (usually, 5% milk) for 60 min at room temp, or overnight at .4°C.
  2. Wash 3 x 5 min with 0.1% Tween 20 in PBS (TBST).
  3. Incubate with secondary antibody diluted in Blocking buffer for one hour at room temp.
  4. Wash 3 x 10 min ( or 4 x 5 min) with TBST.
  5. Detect with Enhanced Chemiluminescence (ECL).

Note: If you want to look into both non-phospho and phosphor-protein with the same blot, make sure to probe the phosphor-antigen first, and be sure you add proper phosphotase inhibitor during the Western blotting procedure due to the high activity of phosphotase. I usually use phosphotase inhibitor cocktail and 50mM sodium floride.

 

I. Stripping blot

  1. Rinse blot off with TBST.
  2. Put blot into Kapak bag cut to slightly bigger size than blot.
  3. Add about 5 to 10 ml Stripping buffer.
  4. Remove as much air as possible and seal bag.
  5. Incubate for 20 min with shaking at 37ºC.
  6. Rinse blot off with TBST.
  7. Repeat step H (1-5) as above.

 

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