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Reviews to Read
Computational approaches to detect allosteric pathways in transmembrane molecular machines

Biochim Biophys Acta. 2016 Jul;1858(7 Pt B):1652-62. doi: 10.1016/j.bbamem.2016.01.010. Epub 2016 Jan 22.

Stolzenberg S, Michino M, LeVine MV, Weinstein H, Shi L.

Many of the functions of transmembrane proteins involved in signal processing and transduction across the cell membrane are determined by allosteric couplings that propagate the functional effects well beyond the original site of activation. Data gathered from breakthroughs in biochemistry, crystallography, and single molecule fluorescence have established a rich basis of information for the study of molecular mechanisms in the allosteric couplings of such transmembrane proteins. The mechanistic details of these couplings, many of which have therapeutic implications, however, have only become accessible in synergy with molecular modeling and simulations. Here, we review some recent computational approaches that analyze allosteric coupling networks (ACNs) in transmembrane proteins...

You can read more about this paper on PubMed.

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Women Scientist Advisors Logo

NIDA IRP NEWS

Congratulations to the 2017 Women Scientist Advisors Committee award winners at the NIDA IRP!

This year's winners at the NIDA IRP are Lindsay De Biase (Postdoctoral Fellow), Jayanthi Sankar (Staff Scientist) and Marisela Morales (Investigator). The winners were presented with trophies at the Biomedical Research Center this month.

Learn more about the Women Scientist Advisors Committee here.

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Study authors William Rea, Ning Sheng Cai and Cesar Quiroz-Molina

Study authors William Rea, Ning Sheng Cai and Cesar Quiroz-Molina

Featured paper of the Month!

May 2017 - Functional μ-Opioid-Galanin Receptor Heteromers in the Ventral Tegmental Area.

J Neurosci. 2017 Feb 1;37(5):1176-1186. doi: 10.1523/JNEUROSCI.2442-16.2016. Epub 2016 Dec 22.

Moreno E, Quiroz C, Rea W, Cai NS, Mallol J, Cortés A, Lluís C, Canela EI, Casadó V, Ferré S.

The neuropeptide galanin has been shown to interact with the opioid system. More specifically, galanin counteracts the behavioral effects of the systemic administration of μ-opioid receptor (MOR) agonists. Yet the mechanism responsible for this galanin-opioid interaction has remained elusive. Using biophysical techniques in mammalian transfected cells, we found evidence for selective heteromerization of MOR and the galanin receptor subtype Gal1 (Gal1R). Also in transfected cells, a synthetic peptide selectively disrupted MOR-Gal1R heteromerization as well as specific interactions between MOR and Gal1R ligands: a negative cross talk, by which galanin counteracted MAPK activation induced by the endogenous MOR agonist endomorphin-1, and a cross-antagonism, by which a MOR antagonist counteracted MAPK activation induced by galanin...

You can read more about this paper on PubMed.

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Da-Ting Lin
Da-Ting Lin

NIDA IRP NEWS

Congratulations to Da-Ting Lin for winning a 2016 Health and Human Services (HHS) Green Champion Award!

Sustainable Acquisitions - Individual
Dr. Da-Ting Lin has worked diligently as an Investigator to integrate sustainable practices into his research using in vivo optical imaging methods. He has prioritized energy conservation, financial savings, and protecting both human and environmental health through his work. He is conscious of the impact his research has on the environment and makes significant efforts to promote sustainability within laboratories. He has worked tirelessly to develop the miniScope imaging system which produces outstanding results while being budget conscious and energy efficient. He incorporated LEDs in the system, which are more environmentally sustainable compared to traditional lights. While making purchasing decisions for his laboratory he prioritizes human health and chooses non-toxic, non-carcinogenic materials. He is also innovative with protocols and avoids mercury in his work. He also promotes awareness of sustainability within the government through staff training and realizes the potential to encourage others to follow his example.

Read more about Dr. Lin's award here.

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Melissa J Sharpe

Hot off the Press paper!

Dopamine transients are sufficient and necessary for
acquisition of model-based associations

Nat Neurosci. 2017 Apr 3. doi: 10.1038/nn.4538. [Epub ahead of print]

Melissa J Sharpe, Chun Yun Chang, Melissa A Liu, Hannah M Batchelor, Lauren E Mueller, Joshua L Jones, Yael Niv & Geoffrey Schoenbaum

Associative learning is driven by prediction errors. Dopamine transients correlate with these errors, which current interpretations limit to endowing cues with a scalar quantity reflecting the value of future rewards. We tested whether dopamine might act more broadly to support learning of an associative model of the environment. Using sensory preconditioning, we show that prediction errors underlying stimulus-stimulus learning can be blocked behaviorally and reinstated by optogenetically activating dopamine neurons. We further show that suppressing the firing of these neurons across the transition prevents normal stimulus-stimulus learning. These results establish that the acquisition of model-based information about transitions between nonrewarding events is also driven by prediction errors and that, contrary to existing canon, dopamine transients are both sufficient and necessary to support this type of learning. Our findings open new possibilities for how these biological signals might support associative learning in the mammalian brain in these and other contexts.

Read more about this paper on PubMed.

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