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Bio4med | Research Projects

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.

Bio4Med Research Projects:


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19: Bio4Med - Vesicular transport machinery in trafficking of ATB(0,+) - amino acid transporter up-regulated in malicious cancer cells
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Supervisor:
prof. Katarzyna Nalecz
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Foreign partner:
Prof. Michael Freissmuth, Medical University of Vienna, Vienna, Austria
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WWW
http://en.nencki.gov.pl/laboratory-for-mechanisms-of-transport-through-biomembranes
Background:
Rapidly proliferating cancer cells need a permanent delivery of nutrients for their growth, such as glucose and amino acids. Out of plethora of amino acid transporters, ATB(0,+) transports all amino acids but the acidic amino acids (glutamate and aspartate) in a Na+/Cl--dependent way. The delivery of many transporters to plasma membrane is regulated post-translationally by vesicular trafficking (and by endocytotic recycling). ATB(0,+) is encoded by SLC6A14 gene, which belongs to a superfamily of genes coding transporters of neurotransmitters, osmolytes and amino acids. Due to their involvement in addiction and psychiatric diseases, the neurotransmitter transporters have been intensively studied with respect to their structure and regulation, including regulation of trafficking. The project will be carried-out in the Nencki Institute of Experimental Biology in Warsaw in the laboratory of Prof. Katarzyna Nałęcz, where the ATB(0,+) coding gene was cloned and heterogously expressed in HEK293 cells. The PhD student is also envisaged to spend at least 3 months in the laboratory of prof. Michael Freissmuth at the Medical University of Vienna. His group has been studying trafficking of neurotransmitter transporters of the SLC6 superfamily, in particular that of SERT (SLC6A4). The project will be focused on regulation of ATB(0,+) trafficking, in particular on identification of proteins involved in this process and finding out their role in transporter regulation. The methods applied in the project include cell culture, molecular biology and techniques used in protein biochemistry, as well as transport measurements (experiments with radioactivity).
Aim:
To verify, (i) which proteins are involved in transporter trafficking to the cell surface and (ii) if ER export of ATB(0,+) is stimulated by growth signals (via AKT-dependent phosphorylation).
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