The success of core laboratories depends in large measure upon the success of the investigators who rely on these laboratories for biotechnological analyses and syntheses. Convincing these investigators that core laboratory staff share a common and equal interest in the success of their studies is a logical and highly effective means to establish and maintain good relationships between staff that work in core laboratories and staff that depend upon these laboratorieswhich inevitably leads to greater understanding when these studies occasionally fail. To routinely succeed requires not only that the core laboratory maintain excellence in terms of its biotechnological capabilities but that the core laboratory understand its own limits and that it conveys these limits to the investigator. Whenever possible, experimental data should be accompanied by an appropriate statistical error analysis, which is often essential to interpret the significance of the data.
In one sense, excellence may be defined by the relative capabilities of other core laboratories and of the theoretical "average core laboratory". For example, if your unit participated in the 1996 Internal Protein Sequence Research Committee study and returned one of the four (out of a total of 41 data sets received and analyzed prior to ABRF '96: Biomolecular Techniques) data sets that correctly sequenced all 15 residues in the target peptide (see page 8 for a short summary of this study), it is probably reasonable to postulate that your internal sequencing capabilities are excellent. This does not, however, guarantee that you will generally succeed at internal sequencing. The latter requires a strong appreciation of the limits within which success is reasonably assured. Hence, successful internal sequencing from a 70 pmol sample subjected to SDS-PAGE (as was the case in the study mentioned above) does not guarantee success when only 10 pmol protein is loaded onto the gel. A resource laboratory that routinely succeeds at internal sequencing of 70 pmol or larger amounts of protein may often fail at the 10 pmol level. Should such a laboratory routinely accept a significant fraction of its samples at this level, it will undoubtedly gain a reputation as being a poor core laboratory when in fact its internal sequencing capabilities may well be excellent in relation to its peers. It is critical therefore that each resource laboratory continually monitor its own capabilities, be ever cognizant of the sample and synthesis request parameters needed to ensure a high rate of success, and convey these data to others.
How can such a core laboratory succeed when confronted with an estimated 10 pmol internal sequencing sample and the knowledge that it requires a significantly larger amount to routinely succeed? One approach is to establish a table that summarizes success rate on past internal sequencing samples as a function of estimated amount of protein submitted and then show it to the submitting investigator. These data will help you and this investigator establish a mutual level of confidence that the core laboratory does indeed routinely succeed in operating at a particular sample level. Encouraged by these data, the investigator may indeed then be willing to return to the bench and purify the larger amount of protein needed to ensure a high probability of success. Often and somewhat surprisingly, the latter can be accomplished in a reasonably short time. If, on the other hand, six months were required to isolate the 10 pmol sample, the core laboratory can still "succeed" if it provides the submitting investigator with a referral to a resource laboratory that (perhaps due to better equipment or to more expertise in this area) may indeed have a better than 90% success rate even at this extremely low level. If the submitting principal investigator prefers to push forward with the "in-house" service, despite, for instance, a past record that indicates only a 25% success rate with this amount of protein, the resource laboratory should be viewed positively regardless of whether sequence data is obtained. That is, if the digest fails under these circumstances, it will merely confirm the validity of the core laboratory's hypothesis.
In closing, we urge all ABRF core laboratories to: continually monitor all their biotechnological capabilities, with active participation in the annual ABRF studies representing one excellent means of accomplishing this task; never cease to further improve these capabilities, with the enormous amount of expertise that exists on ABRF Research Committees representing an extremely useful resource for helping any core laboratory to accomplish this task; and ensure that all core laboratory and non-core laboratory staff are well aware of what is required for routine success.
Ken Williams, Carol Beech, Greg Buck, John Crabb, Karen De Jongh, Nancy Denslow, Lowell Ericsson, Audree Fowler, Elizabeth Fowler, Jay Fox, Gary Hathaway, Tim Hayes, Ulf Hellman, Kathy Ivanetich, Bill Lane, Mark Lively, Dan Marshak, Sheenah Mische, Michael Rohde, John Rush, Clive Slaughter, Al Smith, John Smith, Dave Speicher, and Lynn Williams
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