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UID:917@biology.technion.ac.il

DTSTART;TZID=Asia/Jerusalem:20200907T130000

DTEND;TZID=Asia/Jerusalem:20200907T140000

DTSTAMP:20210802T125901Z

URL:https://biology.technion.ac.il/en/seminars/phd-graduate-seminar-dzmitr
 y-mukha-2/

SUMMARY:PhD. Graduate Seminar-Dzmitry Mukha [No Categories]
DESCRIPTION:Location:   \n Affiliation: \n Host:\n One-carbon(1C) metabolis
 m is highlydysregulated in cancer. While serine serves as the main donor o
 ffolate-mediated 1C units\, recent studies reveal the importance of metabo
 liccontribution by other 1C donors in tumors.Studyingthe contribution of g
 lycine to 1C metabolism\, we found major increase in theexpression of glyc
 ine cleavage system (GCS) genes specifically inhepatocellular carcinoma (H
 CC). We developed a Systems Biology method fordirectly quantifying GCS flu
 x by integrating 13C and 14Ctracers\, and computational modeling – a hig
 hly challenging task considering thevariety of pathways oxidizing glycine 
 and serine\, and the rapid interconversionof these two amino acids. We sho
 w\, for the first time\, that glycine-derived 1Cunits support purine and p
 yrimidine biosynthesis in tumors (via shuttling ofglycine-derived formate 
 to cytosol) and that this occursspecifically in HCC.Geneticsilencing of gl
 ycine decarboxylase (P-subunit of GCS) leads to mitochondrialdysfunction a
 nd halts HCC tumor growth in mouse models. Our work establishesGCS as a no
 vel target for HCC – the most common and highly malignant type ofprimary
  liver cancer\, currently without an effective treatment. 

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DTSTART:20200327T030000

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