Punctuating the genome. Recently Natalia Broude, an ENG research assistant professor at the Center for Advanced Biotechnology, was searching through DNA for specific sequences related to her research when she perceived an unexpected pattern. She enlisted the help of Lingang Zhang, an ENG postdoctoral research assistant. Using a rigorous computational analysis, Zhang supported Broude’s hypothesis: that she had spotted genomic punctuation marks, common characteristics that define transcriptional boundaries, or the beginnings and ends of sequences that control a particular cell process. Further analysis by a research team that also includes ENG Biomedical Engineering Professors Simon Kasif and Charles Cantor confirmed the hypothesis.
Double-stranded DNA is composed of two types of linked molecular pairs — either guanine and cytosine (GC) or adenine and thymine (AT). GC pairs are one and a half times stronger than AT pairs, because three hydrogen bonds hold them together, as opposed to AT’s two. The researchers found that a sharp increase or decrease in the concentration of GC bonds in an area indicates a transcriptional boundary. Correlation between DNA AT/GC content and biological functions has been long suspected, but never subjected to a detailed analysis on a level of thousands of genes.
The researchers analyzed the genomes of six species: humans, mice, rats, chickens, fruit flies, and roundworms. They found that in the four vertebrate species a strong upward spike in the number of GC links indicated the beginning of a transcription sequence, and a strong downward spike in the number of such links marked the end. In the invertebrates (fruit flies and roundworms), the beginning was marked by an upward spike closely followed by a downward spike, and the end by a downward spike followed by an upward spike.
Now that the researchers have confirmed the pattern in silico — by computational methods — Broude and Zhang plan to design laboratory experiments to test if features defined by the patterns on DNA can be linked with specific biological functions. Being able to easily define and find functional genomic sequences will aid researchers to understand how changes in the genome composition affect gene expression and may ultimately lead to a new understanding of the root causes of diseases.
This research was reported in the November 17 issue of the Proceedings of the National Academy of Sciences.
Building healthy structures. With hospitals feeling increasing pressure for a healthy bottom line as well as healthy outcomes for their patients, health-care facilities are increasingly turning to organizational designs and procedures from the business world. However, this may need closer examination, according to a recently published study by SPH Health Services Professor Martin Charns and Associate Professor Gary Young, codirectors of the Program on Health Policy and Management, and SPH Biostatistics Professor Timothy Heeren. They examined the results of implementing a common manufacturing structure — grouping jobs by product rather than function — in 11 general hospitals.
Traditionally hospitals group job positions by function, with distinct departments for nurses, social workers, respiratory therapists, and other professionals. Supervisors in each department have training and expertise in the same skills as the people they supervise. Thus, a cardiac patient is seen by a variety of professionals, each reporting to a different department. The challenge in such a situation is to coordinate care and transmit vital information efficiently and effectively.
In contrast, using a common model in manufacturing known as product line, a product line manager supervises the work of all individuals who produce a particular product or service. In this model a cardiac patient is seen by a team of professionals providing a full spectrum of services, including cardiology, surgery, nursing, rehabilitation, nutrition, and so forth. The SPH researchers note that while care and information is coordinated in this model, the quality of professional services may decline since product line managers may not have the knowledge to make the best decisions in all the professional fields they supervise.
They collected data through employee surveys and site visits, comparing the two structures on performance outcomes (service quality and clinical innovation) and human resource outcomes (professional development and job satisfaction). Although performance outcomes were similar in both structures, a functional structure produced higher levels of skill development and job satisfaction.
The researchers conclude that deficits in skill development and job satisfaction are likely to result in employee turnover — a significant concern in a tight labor market for nurses and other clinical professionals.
This research was published in the October 2004 Academy of Management Journal.
Briefs" is written by Joan Schwartz in the Office of the Provost. To read
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