This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie COFUND grant agreement No 665735.

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17: Bio4Med - Role of stearoyl-CoA desaturase in cardioprotective effects of omega-3 polyunsaturated fatty acids

Supervisor:
prof. Pawel Dobrzyn
Foreign partner:
Prof. Jan Kopecky, Instytute of Physiology CAS, Prague, Czech Republic
WWW
http://heart.nencki.gov.pl/
Background:
Current studies suggest that the omega-3 polyunsaturated fatty acids (omega-3 PUFA) (eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids) may lower the incidence of heart failure. The mechanisms for these potential benefits are complex and not well defined. It is well established that fish oil supplementation lowers plasma triglyceride levels, and more recent work demonstrates anti-inflammatory effects, including reduced circulating levels of inflammatory cytokines and arachidonic acid-derived eicosanoids, and elevated plasma adiponectin. Stearoyl-CoA desaturase (SCD) synthesizes monounsaturated fatty acids that further are elongated to PUFA. Our recent studies established that SCD1 plays an important role in the regulation of cardiac metabolism and function (Dobrzyn et al. 2010 J Lipid Res, Dobrzyn et al. 2015 Prog Lipid Res). The lack of SCD1 expression decreases FA uptake and oxidation and increases glucose transport and oxidation in the heart via PPARalpha dependent mechanism (Dobrzyn et al. 2015). Disruption of the SCD1 gene improves cardiac function in obese leptin-deficient ob/ob mice by correcting the systolic and diastolic dysfunction (Dobrzyn et al. 2010). Our working hypothesis is that lipid signaling networks controlled by SCD are likely to represent critical steps in the maintenance of beneficial omega-3 PUFA action in the heart and, accordingly, cardiac-specific changes in SCD expression/activity can modulate PUFA-signaling in healthy and heart failure states. Specific aims: by using functional genomics (including SCD1 and SCD4 knockout mice) and biochemical approaches we aim to: (1) to determine the functional role of SCD1 and SCD4 in the protective action of omega-3 PUFA in heart failure; (2) to investigate the crosstalk between SCD and omega-3 PUFA in regulation of cardiac bioenergetic metabolism in physiology and in the heart failure.
Aim:
Specific aims: by using functional genomics (including SCD1 and SCD4 knockout mice) and biochemical approaches we aim to: (1) to determine the functional role of SCD1 and SCD4 in the protective action of omega-3 PUFA in heart failure; (2) to investigate the crosstalk between SCD and omega-3 PUFA in regulation of cardiac bioenergetic metabolism in physiology and in the heart failure.
Requirements:
Accomplished Master degree in biotechnology, biology or related field. Excellence in cell and molecular biology tools. Strong and genuine motivation to perform research as well as determination to solve scientific problems. Fluency and clarity in spoken and written English. Candidates must not have resided or carried out their main activity (work, studies, etc.) in Poland for more than 12 months in the past 3 years.