Genome-Scale Identification of Essential Metabolic Processes for Targeting the Plasmodium Liver Stage

Rebecca R. Stanway, Ellen Bushell, Anush Chiappino-Pepe, Magali Roques, Theo Sanderson, Blandine Franke-Fayard, Reto Caldelari, Murielle Golomingi, Mary Nyonda, Vikash Pandey, Frank Schwach, Séverine Chevalley, Jai Ramesar, Tom Metcalf, Colin Herd, Paul Christian Burda, Julian C. Rayner, Dominique Soldati-Favre, Chris J. Janse, Vassily HatzimanikatisOliver Billker*, Volker T. Heussler

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

A genome-scale knockout screen identifies genes important for the entire malaria parasite life cycle and reveals growth bottlenecks in Plasmodium to establish infection in mammalian hosts.

Original languageEnglish
Pages (from-to)1112-1128.e26
JournalCell
Volume179
Issue number5
DOIs
Publication statusPublished - 14 Nov 2019
Externally publishedYes

Bibliographical note

Funding Information:
The authors would like to acknowledge the invaluable assistance of Livia Niklaus, Ruth Rehmann, Mariana De Niz, Francis Brühlmann, Burcu Anar, and Gareth Girling with experimental work and the great input of Aarti Krishnan in the critical reading of the manuscript. We thank Olivier Silvie for providing the modified GOMO gene targeting cassette. D.S., V.T.H., and V.H. were funded by grant 51RTP0_151032 (MalarX), a SystemsX grant awarded by the Swiss National Science foundation (SNSF) , and by an SNSF grant to V.T.H. (grant number 310030_182465 ). Work at the Wellcome Sanger Institute was funded by Wellcome core grant 206194/Z/17/Z awarded to O.B. and J.C.R. Work at Umeå University received funding from the Knut and Alice Wallenberg foundation and the European Research Council (Grant agreement No. 788516 ).

Funding Information:
The authors would like to acknowledge the invaluable assistance of Livia Niklaus, Ruth Rehmann, Mariana De Niz, Francis Br?hlmann, Burcu Anar, and Gareth Girling with experimental work and the great input of Aarti Krishnan in the critical reading of the manuscript. We thank Olivier Silvie for providing the modified GOMO gene targeting cassette. D.S. V.T.H. and V.H. were funded by grant 51RTP0_151032 (MalarX), a SystemsX grant awarded by the Swiss National Science foundation (SNSF), and by an SNSF grant to V.T.H. (grant number 310030_182465). Work at the Wellcome Sanger Institute was funded by Wellcome core grant 206194/Z/17/Z awarded to O.B. and J.C.R. Work at Ume? University received funding from the Knut and Alice Wallenberg foundation and the European Research Council (Grant agreement No. 788516). Conceptualization, V.T.H. O.B. J.C.R. and V.H.; Methodology, R.R.S. E.B. A.C. and T.S.; Software, A.C. T.S. F.S. and V.P.; Formal Analysis, A.C. T.S. F.S. and V.P.; Investigation, R.R.S. E.B. A.C. M.R. B.F. R.C. M.G. M.N. S.C. J.R. T.M. C.H. and P.B.; Writing ? Original Draft, R.R.S. and A.C.; Writing ? Review & Editing, R.R.S. A.C. M.R. C.J.J. O.B. V.T.H. J.C.R. T.S. E.B. D.S. V.H. B.F. R.C. M.N. and P.B.; Visualization; R.R.S. A.C. M.R. O.B. and M.N.; Supervision, V.T.H. R.R.S. E.B. O.B. V.H. C.J.J. and J.C.R.; Project Administration, R.R.S. E.B. M.R. B.F. and C.J.J.; Funding Acquisition, V.T.H. D.S. V.H. O.B. J.C.R. and C.J.J. The authors declare no competing interests.

Publisher Copyright:
© 2019 The Authors

Keywords

  • amino sugar biosynthesis
  • fatty acid biosynthesis
  • fatty acid elongation
  • genome-scale knockout screen
  • genome-scale metabolic model
  • malaria
  • metabolic model
  • metabolic network
  • Plasmodium berghei
  • Plasmodium liver stage

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