Genetic studies, for example, are providing clues for scientists working on vaccines against HIV, malaria, and TB. But it is crucial, say Dave Chokshi (Wellcome Trust Centre for Human Genetics, University of Oxford) and colleagues in a policy paper in PLoS Medicine, to ensure that those who choose to participate in such research have given their fully informed consent.
While there has been much discussion setting out ethical principles for conducting medical research in low-income countries, there has been little discussion of how to apply these principles to large-scale genomic studies. The authors lay out a new set of ethical principles for obtaining ethically valid consent for such studies conducted in the developing world.
Citation: Chokshi DA, Thera MA, Parker M, Diakite M, Makani J, et al. (2007) Valid consent for genomic epidemiology in developing countries. PLoS Med 4(4): e95.
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In this study, they focused on a protein known as steriodogenic factor 1 (SF-1), which is essential for making all steroid hormones. Researchers were interested in discovering what events have to occur in order for SF-1 to bind to DNA.
The first thing they found was that because DNA is so tightly packed in the nucleus, SF-1 can't bind to it until it's unpacked by a group of proteins. Once that happens, SF-1 binds to the genes, beginning the process that makes CYP 17 and ultimately cortisol. But it's not a continuous process, they found.
"Once SF-1 binds, it leaves. A few minutes later other proteins come in and condense the DNA," said Sewer. "After that SF-1 binds again, then leaves, and the proteins cause the DNA to contract again."
This cycle goes on as long as the adrenal gland is receiving the signal.
"Even though you get a sustained production of cortisol, the actual molecular events that happen in the nucleus are dynamic," said Sewer. "It's an extremely complex series of events that starts within minutes of the adrenal gland receiving the signal. Without all these transient binding events, the adrenal gland fails to produce optimal levels of cortisol."
Next the team will investigate how small molecules , ligands , regulate cortisol production by binding to SF-1 and controlling the receptor's ability to bind to DNA.
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