Amazing! Three Nature papers this week…
Cracking the Code: The human body is much more complex than the 20,000 or so genes that are encoded in our DNA. This multiplicity of genetic messages is enhanced by alternative gene splicing, a process where different segments of DNA exons are spliced together to create a different gene message. It is possible to create hundreds of new messages from a single gene. The so called “splicing code” or rules that determines how and where a particular part of a gene is spliced with another segment was deciphered by researchers at the University of Toronto. They can now accurately predict how genetic messages are rearranged on a large scale. Hundreds of different RNA features are taken into account including certain factors in specific tissues to give rise to tissue specific expression. This is an amazing discovery by Drs. Brendan Frey and Benjamin Blencowe that garnered the cover story in this week’s Nature journal.
Stem Cells on Hormones: The ovarian hormone, progesterone, stimulates breast stem cells as its levels peak during the natural reproductive cycle. Researchers observed up to a 14-fold expansion of breast stem cells at peak progesterone levels in a mouse model. This is the first evidence of a direct link between hormones and breast stem cells. Since cancers are thought to initiate from stem cells, if there are other oncogenic factors pushing the system this may be a critical point that ultimately drives the start of a cancer. There are implications of this study to further understanding how reproductive history is a strong risk factor for breast cancer and may lead to therapeutic intervention. The research team at Princess Margaret Hospital, University Health Network was led by Dr. Rama Khokha and describes their work in Nature.
Reversing HER2 Breast Cancer: Through genomic studies of HER2 positive breast cancer, it was noted that the 14-3-3sigma gene was frequently missing. After several years of hard work focusing on this gene, researchers have demonstrated that the 14-3-3sigma gene does indeed play a specific role in the development and function of breast epithelial tissue. In the absence of 14-3-3sigma, the normally organized and polarized sheets of epithelial cells clump together and lose polarity. It is this loss of organization without 14-3-3sigma that likely contributes to breast cancer progression. From a therapeutic standpoint, the reintroduction of 14-3-3sigma into HER2 positive breast cancer cells resulted in the restoration of cell polarity and opens a window for further studies as a pathway to target. Dr. William Muller (my former mentor) and his team at McGill University describe their research in the early edition of Genes and Development.
Bionic Muscle: Artificial proteins were assembled together in a fashion that mimics the molecular spring structure of a muscle protein called Titin, which is a very large protein that gives muscle tissue its unique properties of strength, extensibility and resilience. This is why muscle has superior elasticity. The biomaterial looks like a string of beads and although it exhibits only some of the mechanical characteristics of muscle tissue, its structure can be adjusted to provide specific properties of different types of muscle. There are obvious future applications of this technology in regenerative medicine and tissue engineering. Drs. Hongbin Li and John Gosline at the University of British Columbia present their work in this week’s Nature journal.