The Cross-Border Biotech Blog

Biotechnology, Health and Business in Canada, the United States and Worldwide

Friday Science Review: July 15, 2011

New Target for AML

British Columbia Cancer Agency ♦ University of British Columbia ♦ Hannover Medical School ♦ Stanford University School of Medicine

Published in Cancer Cell, July 12, 2011

The MN1 locus is implicated in the development of acute myeloid leukemia (AML), where its up-regulation is a poor prognostic marker. Not all progenitors are transformed by MN1 over-expression though; common myeloid progenitors, rather than granulocyte-macrophage progenitors, are susceptible. In this study, researchers began to elucidate the genetic programs that underlie susceptibility to MN1 transformation. Complementation studies showed that MN1 required the MEIS1/AbdB-like HOX-protein complex to drive transformation. Chromatin immuno-precipitation illustrates that MN1 and MEIS1 have many identical chromatin targets, suggesting the two work together in some fashion to promote AML. Although MN1 relies on MEIS1 for transformation, it cannot activate expression of the complex, so transcriptional repression of MEIS1 could be an effective treatment paradigm for MN1-induced AML down the line.

De Novo Mutations in Non-Familial Schizophrenia

University of Montreal ♦ McGill University ♦ University of Hong Kong ♦ Others..

Published in Nature Genetics, July 10, 2011

In an eloquent study, researchers have identified a group of genes that could be responsible in part for the development of schizophrenia. The study involved 14 ‘trios’, including 14 schizophrenia patients and their parents. By focusing on non-familial cases (none of the patients had first- or second- degree family history of psychotic disorders), it could be assumed that the primary genetic events driving pathogenesis were the de novo mutations (DNMs)  occurring in the genomes of the patients themselves. The exomes of the 14 patients were sequenced which led to the identification of 15 DNMs in 8 of the patients, a much greater rate than previously reported. These findings suggest DNMs may contribute to the heritability of the disease and provide a list of targets for future consideration.

Mechanism of Carvedilol Elucidated

University of Calgary ♦ Rush University ♦ University of Iowa ♦ Thomas Jefferson University ♦ UC San Diego ♦ Others..

Published in Nature Medicine, July 10, 2011

One of the most potent beta blockers for the treatment of heart failure is carvedilol, however until now its mechanism of action was largely unknown. Researchers show that the small molecule suppresses a process known as store overload-induced calcium release (SOICR). When patients have tachyarryhythmias leading to heart failure, SOICR is usually the cause, and carvedilol was the only beta blocker under investigation that could suppress this calcium release. Carvedilol exerts its effects by reducing the period of time that cardiac ryanodine receptors are open for, and hence the amount of calcium that is released, preventing arrhythmia. To further investigate carvedilol’s SOICR-suppressing capabilities, researchers constructed an analog with vastly reduced beta blocking capacity and showed that it prevented stress induced ventricular tachyarrhythmias in mice. Combining the analog with selective beta blockers, like metoprolol or bisoprolol, produced optimal effects.

Using DNA to Program Quantum Dot Self-Assembly

University of Toronto ♦ Published in Nature Nanotechnology, July 10, 2011

Shana Kelley’s lab has impressed once again with this paper that illustrates how DNA can be used to not only guide the self-assembly of quantum dots, but regulate a series of properties that are crucial to their function in areas such as optical detection, solar energy harvesting, and biological research. Ideally quantum dots exhibit high luminescence efficiency, spectral tunability, control over valency (how many quantum dots a single dot is connected with), and bonding control. In this study, researchers constructed nanocrystals from cadmium telluride and capped them with specific sequences of DNA. The strategy for developing these ideal dots involved varying the brightness of dots, size of dots, the number of DNA strands per dot, and the sequences of those DNA strands. Combining these elements allows for broader functionality and a myriad of different construction possibilities, including cross-shaped forms containing three different dots. Although DNA-functionalized quantum dots have been made before, this is the first time they have been constructed with control over valency and other properties. Quantum dots can be switched on and off as well; modulating pH can alter conformation and the transfer of energy between dots in higher-order complexes.

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