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Norbert Perrimon

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Norbert Perrimon
Born (1958-10-24) October 24, 1958 (age 66) [2]
Bosguérard-de-Marcouville[2]
NationalityFrench
CitizenshipFrance, United States
Alma materUniversity of Paris
Known forGAL4/UAS system
AwardsGeorge W. Beadle Award (2004)[1]
Scientific career
Institutions
ThesisAnalyse Clonale de Mutations en Lignee Germinale chez la Drosophile (1983)
Academic advisorsMadeleine Gans
Notable studentsSara Cherry
Website

Norbert Perrimon is a French geneticist and developmental biologist. He is the James Stillman Professor of Developmental Biology in the Department of Genetics at Harvard Medical School, an Investigator at the Howard Hughes Medical Institute, and an Associate of the Broad Institute. He is known for developing a number of techniques for used in genetic research with Drosophila melanogaster, as well as specific substantive contributions to signal transduction, developmental biology and physiology.

Perrimon has authored over 400 peer-reviewed publications, with an H-index exceeding 150.[3]

Education

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Perrimon was born in 1958 in Bosguérard-de-Marcouville, France. He earned his undergraduate degree (Maitrise of Biochemistry) at the University of Paris VI, in 1981, then completed his doctorate in 1983 with Madeleine Gans, also at the University of Paris.

Career

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From 1983 to 1986 Perrimon was a postdoctoral researcher with Anthony Mahowald[4][5][6][7] at Case Western Reserve University, and in 1986 at the age of 27 he accepted an appointment as faculty at Harvard Medical School. He is currently the James Stillman Professor of Developmental Biology in the Department of Genetics at Harvard Medical School. He has been an Investigator of the Howard Hughes Medical Institute since 1986.[8]

Research

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Dominant Female Sterile Technique and Maternal-Effect Mutations

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The FLP-FRT Dominant Female Sterile (DFS) technique was developed by Norbert Perrimon and Tze-bin Chou to produce germline mosaics in Drosophila melanogaster. The method enables gene manipulation in germline cells while leaving somatic cells unaffected.[9] This technique addressed limitations in studying zygotic lethal mutations, which prevent organisms from surviving to adulthood. By generating mosaic germlines, researchers were able to examine the function of essential genes during early embryogenesis.[10][11]

GAL4/UAS System

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The GAL4/UAS system was introduced by Perrimon and Andrea Brand as a binary method for controlling gene expression in Drosophila. It employs the yeast transcription factor GAL4, which activates genes placed downstream of Upstream Activating Sequences (UAS).[12]

By combining GAL4 drivers under tissue-specific or inducible promoters with UAS-linked transgenes, gene expression can be regulated spatially and temporally. Variants such as GAL80^ts and other binary systems (e.g., LexA/LexAop) have expanded its applicability.[13]

Developmental Signaling Pathways

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Using the DFS technique, genetic screens were conducted to identify maternal-effect genes involved in embryonic patterning. These studies contributed to the identification of components in several conserved signaling pathways, including Receptor Tyrosine Kinases (RTKs), JAK/STAT, Wnt/Wingless, JNK, Hedgehog, and Notch.

The work helped define mechanisms of cell signaling and pattern formation in early Drosophila development. Many of these pathways are evolutionarily conserved and play roles in tissue specification and morphogenesis.

Genome-Wide RNAi Screens

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Genome-wide RNA interference (RNAi) screening was adapted for Drosophila cell lines in studies led by Perrimon. These high-throughput approaches allowed systematic analysis of gene function across a range of cellular processes, including signal transduction and host-pathogen interactions.[14][15]

To support these efforts, the Drosophila RNAi Screening Center (DRSC) was established in 2003, followed by the Transgenic RNAi Project (TRiP) in 2008. The latter generated RNAi lines for in vivo gene knockdown using short hairpin RNA (shRNA) vectors. These resources have been used in studies of development and physiology.[16]

Intestinal Stem Cells and Gut Homeostasis

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In 2006, intestinal stem cells (ISCs) were identified in the adult Drosophila midgut by Perrimon and Craig Micchelli, in parallel with work from Alan Spradling’s laboratory. This model system has been used to study stem cell maintenance, lineage specification, and tissue regeneration.[17][18][19][20]

Subsequent research has examined how stem cell function is influenced by age, injury, diet, and microbiota. The system has also been used to study the regulation of tissue homeostasis and disease-related processes.[21][22]

Inter-Organ Communication

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Research in Drosophila has been used to study inter-organ communication, particularly how physiological signals coordinate growth and metabolism.[23] Studies have identified secreted factors and pathways including insulin, TOR, and JAK/STAT that mediate signaling between tissues such as the fat body, gut, muscle, and brain.[24]

This research has provided insight into how organisms regulate nutrient use and respond to environmental changes. Drosophila models have also been used to study conditions involving tissue wasting, such as cachexia.[25]

Pooled CRISPR Screens in Arthropods

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Pooled CRISPR/Cas9 screening methods were developed for Drosophila cell lines in collaboration between Perrimon and Ram Viswanatha. These techniques allow genome-wide functional analysis through high-throughput CRISPR-based editing.[26]

This approach has been applied to study gene function in various biological contexts, including toxin susceptibility and host-pathogen interactions. The method has extended CRISPR screening capabilities to non-mammalian systems, including other arthropods.[27]

Awards and honors

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Perrimon was elected to the United States National Academy of Sciences in April 2013,[19][28] after naturalizing as an American citizen.

References

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  1. ^ a b Schüpbach, T. (2004). "The 2004 George W. Beadle Medal". Genetics. 166 (2): 649–650. doi:10.1534/genetics.166.2.649. PMC 1470725. PMID 15020455.
  2. ^ a b "Archived copy". Archived from the original on 2014-08-08. Retrieved 2014-08-07.{{cite web}}: CS1 maint: archived copy as title (link)
  3. ^ "Norbert Perrimon | American Academy of Arts and Sciences". www.amacad.org. 2025-05-02. Retrieved 2025-05-02.
  4. ^ Perrimon, N; Engstrom, L; Mahowald, A. P. (1985). "Developmental genetics of the 2C-D region of the Drosophila X chromosome". Genetics. 111 (1): 23–41. doi:10.1093/genetics/111.1.23. PMC 1202596. PMID 3928431.
  5. ^ Perrimon, N; Mohler, D; Engstrom, L; Mahowald, A. P. (1986). "X-linked female-sterile loci in Drosophila melanogaster". Genetics. 113 (3): 695–712. doi:10.1093/genetics/113.3.695. PMC 1202863. PMID 3089870.
  6. ^ Perrimon, N; Mahowald, A. P. (1986). "L(1)hopscotch, A larval-pupal zygotic lethal with a specific maternal effect on segmentation in Drosophila". Developmental Biology. 118 (1): 28–41. doi:10.1016/0012-1606(86)90070-9. PMID 3095163.
  7. ^ Perrimon, N; Mahowald, A. P. (1987). "Multiple functions of segment polarity genes in Drosophila". Developmental Biology. 119 (2): 587–600. doi:10.1016/0012-1606(87)90061-3. PMID 3803719.
  8. ^ "Norbert Perrimon, PhD | HHMI.org". HHMI.org. Retrieved 2016-11-21.
  9. ^ Chou, T. B.; Perrimon, N. (1992-07-01). "Use of a yeast site-specific recombinase to produce female germline chimeras in Drosophila". Genetics. 131 (3): 643–653. doi:10.1093/genetics/131.3.643. ISSN 0016-6731. PMC 1205036. PMID 1628809.
  10. ^ Chou, T. B.; Noll, E.; Perrimon, N. (1993-12-01). "Autosomal P[ovoD1] dominant female-sterile insertions in Drosophila and their use in generating germ-line chimeras". Development. 119 (4): 1359–1369. doi:10.1242/dev.119.4.1359. ISSN 0950-1991. PMID 8306893.
  11. ^ Chou, Tze-bin; Perrimon, Norbert (1996-12-01). "The Autosomal FLP-DFS Technique for Generating Germline Mosaics in Drosophila melanogaster". Genetics. 144 (4): 1673–1679. doi:10.1093/genetics/144.4.1673. ISSN 0016-6731. PMC 1207718. PMID 8978054.
  12. ^ Brand, A. H.; Perrimon, N. (1993). "Targeted gene expression as a means of altering cell fates and generating dominant phenotypes". Development. 118 (2): 401–415. doi:10.1242/dev.118.2.401. PMID 8223268.
  13. ^ Shetty, P. (2008). "Molecular biologist Andrea Brand: encouraging women in science". The Lancet. 371 (9617): 979. doi:10.1016/S0140-6736(08)60439-0. PMID 18358916. S2CID 33668220.
  14. ^ Ni, Jian-Quan; Markstein, Michele; Binari, Richard; Pfeiffer, Barret; Liu, Lu-Ping; Villalta, Christians; Booker, Matthew; Perkins, Lizabeth; Perrimon, Norbert (2008-01-01). "Vector and parameters for targeted transgenic RNA interference in Drosophila melanogaster". Nature Methods. 5 (1): 49–51. doi:10.1038/nmeth1146. ISSN 1548-7091. PMC 2290002. PMID 18084299.
  15. ^ Ni, Jian-Quan; Liu, Lu-Ping; Binari, Richard; Hardy, Robert; Shim, Hye-Seok; Cavallaro, Amanda; Booker, Matthew; Pfeiffer, Barret D.; Markstein, Michele (2009-08-01). "A Drosophila resource of transgenic RNAi lines for neurogenetics". Genetics. 182 (4): 1089–1100. doi:10.1534/genetics.109.103630. ISSN 1943-2631. PMC 2728850. PMID 19487563.
  16. ^ Ni, Jian-Quan; Zhou, Rui; Czech, Benjamin; Liu, Lu-Ping; Holderbaum, Laura; Yang-Zhou, Donghui; Shim, Hye-Seok; Tao, Rong; Handler, Dominik (2011-05-01). "A genome-scale shRNA resource for transgenic RNAi in Drosophila". Nature Methods. 8 (5): 405–407. doi:10.1038/nmeth.1592. ISSN 1548-7105. PMC 3489273. PMID 21460824.
  17. ^ Boutros, Michael; Kiger, Amy A.; Armknecht, Susan; Kerr, Kim; Hild, Marc; Koch, Britta; Haas, Stefan A.; Paro, Renato; Perrimon, Norbert; Heidelberg Fly Array Consortium (2004-02-06). "Genome-wide RNAi analysis of growth and viability in Drosophila cells". Science. 303 (5659): 832–835. doi:10.1126/science.1091266. ISSN 1095-9203. PMID 14764878.
  18. ^ Perrimon, N. (2005). "Norbert Perrimon". Current Biology. 15 (13): R481 – R482. doi:10.1016/j.cub.2005.06.050. PMID 16059997. S2CID 34889938.
  19. ^ a b Ravindran, S (2014). "Profile of Norbert Perrimon". Proceedings of the National Academy of Sciences. 111 (21): 7501–2. Bibcode:2014PNAS..111.7501R. doi:10.1073/pnas.1406464111. PMC 4040556. PMID 24778217.
  20. ^ White, R. A.; Perrimon, N; Gehring, W. J. (1984). "Differentiation markers in the Drosophila ovary". Journal of Embryology and Experimental Morphology. 84: 275–86. PMID 6442733.
  21. ^ Perrimon, N; Gans, M (1983). "Clonal analysis of the tissue specificity of recessive female-sterile mutations of Drosophila melanogaster using a dominant female-sterile mutation Fs(1)K1237". Developmental Biology. 100 (2): 365–73. doi:10.1016/0012-1606(83)90231-2. PMID 6418585.
  22. ^ Perrimon, N (1984). "Clonal Analysis of Dominant Female-Sterile, Germline-Dependent Mutations in DROSOPHILA MELANOGASTER". Genetics. 108 (4): 927–39. doi:10.1093/genetics/108.4.927. PMC 1224274. PMID 17246244.
  23. ^ Perrimon, N.; Engstrom, L.; Mahowald, A. P. (1984). "The effects of zygotic lethal mutations on female germ-line functions in Drosophila". Developmental Biology. 105 (2): 404–414. doi:10.1016/0012-1606(84)90297-5. PMID 6479445.
  24. ^ Droujinine, Ilia A.; Perrimon, Norbert (2016-11-23). "Interorgan Communication Pathways in Physiology: Focus on Drosophila". Annual Review of Genetics. 50: 539–570. doi:10.1146/annurev-genet-121415-122024. ISSN 1545-2948. PMC 5506552. PMID 27732790.
  25. ^ "Drosophila as a model for interorgan communication: lessons from studies on energy homeostasis. | Laboratory of Norbert Perrimon, Ph.D." perrimon.med.harvard.edu. Retrieved 2025-05-02.
  26. ^ Viswanatha, Raghuvir; Li, Zhongchi; Hu, Yanhui; Perrimon, Norbert (2018-07-27). "Pooled genome-wide CRISPR screening for basal and context-specific fitness gene essentiality in Drosophila cells". eLife. 7: e36333. doi:10.7554/eLife.36333. ISSN 2050-084X. PMC 6063728. PMID 30051818.
  27. ^ Xu, Ying; Viswanatha, Raghuvir; Sitsel, Oleg; Roderer, Daniel; Zhao, Haifang; Ashwood, Christopher; Voelcker, Cecilia; Tian, Songhai; Raunser, Stefan; Perrimon, Norbert; Dong, Min (October 2022). "CRISPR screens in Drosophila cells identify Vsg as a Tc toxin receptor". Nature. 610 (7931): 349–355. doi:10.1038/s41586-022-05250-7. ISSN 1476-4687. PMC 9631961. PMID 36171290.
  28. ^ "April 30, 2013, NAS Election", National Academy of Sciences (last visited May 3, 2013).
  29. ^ Teltsch, Kathleen (1985-02-10). "16 ARE GIVEN MARKEY RESEARCH SCHOLARSHIPS". The New York Times. ISSN 0362-4331. Retrieved 2023-08-28.
  30. ^ "Innovator Award Recipients". www.expressgenes.com. GeneExpression Systems. Retrieved 31 October 2016.
  31. ^ "Member Directory | American Academy of Arts and Sciences". www.amacad.org. Retrieved 2023-09-12.
  32. ^ Reuell, Peter (2018-10-31). "Seven Harvard researchers receive NIH funding for high-risk, high-reward research". Harvard Gazette. Retrieved 2025-05-02.
  33. ^ "HSCI scientists receive "High-Risk, High-Reward" awards". www.hsci.harvard.edu. Retrieved 2025-05-02.
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