Laboratory Notebook: Mail from Cal [Calvin Harvey], 1989 - 1992

Much of the notebook is an email and letter exchange between Harley and Greider. Begins with good news, as the ribosomel RNA probe that she used seemed to have worked on the blots but not the gels. There is some bad news however, such as shattered tubes, and samples of DNA that have been used up. Grieder gave suggestions on how to run the remaining samples. Harley’s response was that Harley was analyzing telomere activity in the brain, specifically those with alzhiemers. The deeper the layer of the brain or the cortex, the shorter the telomere. Certain areas of the brain, like the olfactory bulb have longer telomeres. Possible candidate for finding telomerase in the brain of humans. Possibly even 11 to 12 kilobases. And subject was 80 years old. Greider wanted to submit the article with new data from the unique sequence probe. If the probe showed shortening of telomeres then they will send it out. But if not, then the authors of the article would withdraw the paper and submit to a different journal regardless of the outcome of the probe. However, Harley wanting to understand the order, titles, and authors. In terms of Harley's research, Harley wanted to understand the loss of telomeric DNA during aging of human fibroblasts. The telomere was shortening during aging and considered using a different test for the model, opting to probe with T2AG3 and C3TA2 and then compare size distributions. Harely thought C3TA2 probe should detect longer telomeres. Harley found that during aging, the TTAGGG repeat is lost. Harley was worried about their work being scooped. Harley did not think anyone else has done what they have done. Other groups (Hastie and Cook) have been looking for telomere activity in fetal and adult forms.

Greider discusses their problems, such as the number of possible mechanisms for loss of telomeric DNA during aging, with other researchers familiar with the issue. She thinks the possible meachanims are incomplete replication, degradation of termini (specific and nonspecific), and unequal recombination coupled with selection of cells with shorter telomeres. She realizes that further research is required to determine the mechanism of telomere shortening in human fibroblasts and significance to cellular senescence She also reviews her manuscript with Carol on human fibrobast telomeres. Calvin responds, having found two big observations with vein endothelial cells cultured from the same individual have shorter telomeres and vein telomeres are longer than artery telomeres. The bar graphs that he includes show the mean lengths of the terminal restriction fragment (TRF) of DNA versus the age of donor. The bar graph also includes calculations.