Norbert Perrimon

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.

From 1983 to 1986 Perrimon was a postdoctoral researcher with Anthony Mahowald{{Cite journal

| pmid = 3928431

| year = 1985

| last1 = Perrimon

| first1 = N

| title = Developmental genetics of the 2C-D region of the Drosophila X chromosome

| journal = Genetics

| volume = 111

| issue = 1

| pages = 23–41

| last2 = Engstrom

| first2 = L

| last3 = Mahowald

| first3 = A. P.

| doi = 10.1093/genetics/111.1.23

| pmc = 1202596

}}{{Cite journal

| pmid = 3089870

| year = 1986

| last1 = Perrimon

| first1 = N

| title = X-linked female-sterile loci in Drosophila melanogaster

| journal = Genetics

| volume = 113

| issue = 3

| pages = 695–712

| last2 = Mohler

| first2 = D

| last3 = Engstrom

| first3 = L

| last4 = Mahowald

| first4 = A. P.

| doi = 10.1093/genetics/113.3.695

| pmc = 1202863

}}{{Cite journal

| pmid = 3095163

| year = 1986

| last1 = Perrimon

| first1 = N

| title = L(1)hopscotch, A larval-pupal zygotic lethal with a specific maternal effect on segmentation in Drosophila

| journal = Developmental Biology

| volume = 118

| issue = 1

| pages = 28–41

| last2 = Mahowald

| first2 = A. P.

| doi=10.1016/0012-1606(86)90070-9

}}{{Cite journal

| pmid = 3803719

| year = 1987

| last1 = Perrimon

| first1 = N

| title = Multiple functions of segment polarity genes in Drosophila

| journal = Developmental Biology

| volume = 119

| issue = 2

| pages = 587–600

| last2 = Mahowald

| first2 = A. P.

| doi=10.1016/0012-1606(87)90061-3

}} at Case Western Reserve University, and in 1986 at the age of {{#expr:(1986)-(1958)-((0)<(10)or(0)=(10)and(0)<(24))}} 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.{{Cite news|url=http://www.hhmi.org/scientists/norbert-perrimon|title=Norbert Perrimon, PhD {{!}} HHMI.org|newspaper=HHMI.org|access-date=2016-11-21}}

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.{{Cite journal |last1=Chou |first1=T. B. |last2=Perrimon |first2=N. |date=1992-07-01 |title=Use of a yeast site-specific recombinase to produce female germline chimeras in Drosophila. |url=http://www.genetics.org/content/131/3/643 |journal=Genetics |language=en |volume=131 |issue=3 |pages=643–653 |doi=10.1093/genetics/131.3.643 |issn=0016-6731 |pmc=1205036 |pmid=1628809}} 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.{{Cite journal |last1=Chou |first1=T. B. |last2=Noll |first2=E. |last3=Perrimon |first3=N. |date=1993-12-01 |title=Autosomal P[ovoD1] dominant female-sterile insertions in Drosophila and their use in generating germ-line chimeras |url=http://dev.biologists.org/content/119/4/1359 |journal=Development |language=en |volume=119 |issue=4 |pages=1359–1369 |doi=10.1242/dev.119.4.1359 |issn=0950-1991 |pmid=8306893|url-access=subscription }}{{Cite journal |last1=Chou |first1=Tze-bin |last2=Perrimon |first2=Norbert |date=1996-12-01 |title=The Autosomal FLP-DFS Technique for Generating Germline Mosaics in Drosophila melanogaster |url=http://www.genetics.org/content/144/4/1673 |journal=Genetics |language=en |volume=144 |issue=4 |pages=1673–1679 |doi=10.1093/genetics/144.4.1673 |issn=0016-6731 |pmc=1207718 |pmid=8978054}}

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).{{Cite journal |last1=Brand |first1=A. H. |last2=Perrimon |first2=N. |year=1993 |title=Targeted gene expression as a means of altering cell fates and generating dominant phenotypes |url=http://dev.biologists.org/content/118/2/401.long |journal=Development |volume=118 |issue=2 |pages=401–415 |doi=10.1242/dev.118.2.401 |pmid=8223268 |authorlink1=Andrea Brand |authorlink2=Norbert Perrimon|url-access=subscription }}

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.{{Cite journal |last1=Shetty |first1=P. |year=2008 |title=Molecular biologist Andrea Brand: encouraging women in science |journal=The Lancet |volume=371 |issue=9617 |pages=979 |doi=10.1016/S0140-6736(08)60439-0 |pmid=18358916 |s2cid=33668220}}

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 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.{{Cite journal |last1=Ni |first1=Jian-Quan |last2=Markstein |first2=Michele |last3=Binari |first3=Richard |last4=Pfeiffer |first4=Barret |last5=Liu |first5=Lu-Ping |last6=Villalta |first6=Christians |last7=Booker |first7=Matthew |last8=Perkins |first8=Lizabeth |last9=Perrimon |first9=Norbert |date=2008-01-01 |title=Vector and parameters for targeted transgenic RNA interference in Drosophila melanogaster |journal=Nature Methods |language=en |volume=5 |issue=1 |pages=49–51 |doi=10.1038/nmeth1146 |issn=1548-7091 |pmc=2290002 |pmid=18084299}}{{Cite journal |last1=Ni |first1=Jian-Quan |last2=Liu |first2=Lu-Ping |last3=Binari |first3=Richard |last4=Hardy |first4=Robert |last5=Shim |first5=Hye-Seok |last6=Cavallaro |first6=Amanda |last7=Booker |first7=Matthew |last8=Pfeiffer |first8=Barret D. |last9=Markstein |first9=Michele |date=2009-08-01 |title=A Drosophila resource of transgenic RNAi lines for neurogenetics |journal=Genetics |volume=182 |issue=4 |pages=1089–1100 |doi=10.1534/genetics.109.103630 |issn=1943-2631 |pmc=2728850 |pmid=19487563}}

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.{{Cite journal |last1=Ni |first1=Jian-Quan |last2=Zhou |first2=Rui |last3=Czech |first3=Benjamin |last4=Liu |first4=Lu-Ping |last5=Holderbaum |first5=Laura |last6=Yang-Zhou |first6=Donghui |last7=Shim |first7=Hye-Seok |last8=Tao |first8=Rong |last9=Handler |first9=Dominik |date=2011-05-01 |title=A genome-scale shRNA resource for transgenic RNAi in Drosophila |journal=Nature Methods |volume=8 |issue=5 |pages=405–407 |doi=10.1038/nmeth.1592 |issn=1548-7105 |pmc=3489273 |pmid=21460824}}

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.{{Cite journal |last1=Boutros |first1=Michael |last2=Kiger |first2=Amy A. |last3=Armknecht |first3=Susan |last4=Kerr |first4=Kim |last5=Hild |first5=Marc |last6=Koch |first6=Britta |last7=Haas |first7=Stefan A. |last8=Paro |first8=Renato |last9=Perrimon |first9=Norbert |last10=Heidelberg Fly Array Consortium |date=2004-02-06 |title=Genome-wide RNAi analysis of growth and viability in Drosophila cells |url=https://pubmed.ncbi.nlm.nih.gov/14764878 |journal=Science |volume=303 |issue=5659 |pages=832–835 |doi=10.1126/science.1091266 |issn=1095-9203 |pmid=14764878}}{{Cite journal |last1=Perrimon |first1=N. |year=2005 |title=Norbert Perrimon |journal=Current Biology |volume=15 |issue=13 |pages=R481–R482 |doi=10.1016/j.cub.2005.06.050 |pmid=16059997 |s2cid=34889938 |doi-access=free}}{{Cite journal |last1=Ravindran |first1=S |year=2014 |title=Profile of Norbert Perrimon |journal=Proceedings of the National Academy of Sciences |volume=111 |issue=21 |pages=7501–2 |bibcode=2014PNAS..111.7501R |doi=10.1073/pnas.1406464111 |pmc=4040556 |pmid=24778217 |doi-access=free}}{{Cite journal |last1=White |first1=R. A. |last2=Perrimon |first2=N |last3=Gehring |first3=W. J. |year=1984 |title=Differentiation markers in the Drosophila ovary |journal=Journal of Embryology and Experimental Morphology |volume=84 |pages=275–86 |pmid=6442733}}

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.{{Cite journal |last1=Perrimon |first1=N |last2=Gans |first2=M |year=1983 |title=Clonal analysis of the tissue specificity of recessive female-sterile mutations of Drosophila melanogaster using a dominant female-sterile mutation Fs(1)K1237 |journal=Developmental Biology |volume=100 |issue=2 |pages=365–73 |doi=10.1016/0012-1606(83)90231-2 |pmid=6418585}}{{Cite journal |last1=Perrimon |first1=N |year=1984 |title=Clonal Analysis of Dominant Female-Sterile, Germline-Dependent Mutations in DROSOPHILA MELANOGASTER |journal=Genetics |volume=108 |issue=4 |pages=927–39 |doi=10.1093/genetics/108.4.927 |pmc=1224274 |pmid=17246244}}

Research in Drosophila has been used to study inter-organ communication, particularly how physiological signals coordinate growth and metabolism.{{Cite journal |last1=Perrimon |first1=N. |last2=Engstrom |first2=L. |last3=Mahowald |first3=A. P. |year=1984 |title=The effects of zygotic lethal mutations on female germ-line functions in Drosophila |journal=Developmental Biology |volume=105 |issue=2 |pages=404–414 |doi=10.1016/0012-1606(84)90297-5 |pmid=6479445}} 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.{{Cite journal |last=Droujinine |first=Ilia A. |last2=Perrimon |first2=Norbert |date=2016-11-23 |title=Interorgan Communication Pathways in Physiology: Focus on Drosophila |url=https://pmc.ncbi.nlm.nih.gov/articles/PMC5506552/ |journal=Annual Review of Genetics |volume=50 |pages=539–570 |doi=10.1146/annurev-genet-121415-122024 |issn=1545-2948 |pmc=5506552 |pmid=27732790}}

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.{{Cite web |title=Drosophila as a model for interorgan communication: lessons from studies on energy homeostasis. {{!}} Laboratory of Norbert Perrimon, Ph.D. |url=https://perrimon.med.harvard.edu/publications/drosophila-model-interorgan-communication-lessons-studies-energy |access-date=2025-05-02 |website=perrimon.med.harvard.edu |language=en}}

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.{{Cite journal |last1=Viswanatha |first1=Raghuvir |last2=Li |first2=Zhongchi |last3=Hu |first3=Yanhui |last4=Perrimon |first4=Norbert |date=2018-07-27 |title=Pooled genome-wide CRISPR screening for basal and context-specific fitness gene essentiality in Drosophila cells |journal=eLife |volume=7 |pages=e36333 |doi=10.7554/eLife.36333 |issn=2050-084X |pmc=6063728 |pmid=30051818 |doi-access=free}}

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.{{Cite journal |last1=Xu |first1=Ying |last2=Viswanatha |first2=Raghuvir |last3=Sitsel |first3=Oleg |last4=Roderer |first4=Daniel |last5=Zhao |first5=Haifang |last6=Ashwood |first6=Christopher |last7=Voelcker |first7=Cecilia |last8=Tian |first8=Songhai |last9=Raunser |first9=Stefan |last10=Perrimon |first10=Norbert |last11=Dong |first11=Min |date=October 2022 |title=CRISPR screens in Drosophila cells identify Vsg as a Tc toxin receptor |journal=Nature |volume=610 |issue=7931 |pages=349–355 |doi=10.1038/s41586-022-05250-7 |issn=1476-4687 |pmc=9631961 |pmid=36171290}}

Perrimon was elected to the United States National Academy of Sciences in April 2013,[http://www.nasonline.org/news-and-multimedia/news/2013_04_30_NAS_Election.html "April 30, 2013, NAS Election"], National Academy of Sciences (last visited May 3, 2013). after naturalizing as an American citizen.

• Lucille P. Markey Scholar in Biomedical Sciences, 1985.{{Cite news |last=Teltsch |first=Kathleen |date=1985-02-10 |title=16 ARE GIVEN MARKEY RESEARCH SCHOLARSHIPS |language=en-US |work=The New York Times |url=https://www.nytimes.com/1985/02/10/us/16-are-given-markey-research-scholarships.html |access-date=2023-08-28 |issn=0362-4331}}
• Investigator, Howard Hughes Medical Institute, 1986–present
• Chaire d’Etat. College de France. Paris, 2003
• George W. Beadle Medal, Genetics Society of America, 2004
• RNAi Innovator Award, 2009{{cite web|title=Innovator Award Recipients|url=http://www.expressgenes.com/innovator-pix.htm|website=www.expressgenes.com|publisher=GeneExpression Systems|access-date=31 October 2016}}
• Fellow of the American Academy of Arts and Sciences, 2008{{Cite web |title=Member Directory {{!}} American Academy of Arts and Sciences |url=https://www.amacad.org/directory?search_api_fulltext=norbert%20perrimon&field_class_section=All&field_class_section_1=All&field_deceased=All&sort_bef_combine=search_api_relevance_DESC |access-date=2023-09-12 |website=www.amacad.org}}
• Fellow of the American Association for the Advancement of Science, 2009
• Associate member of the European Molecular Biology Organization (EMBO) 2011
• Fellow of the United States National Academy of Sciences, 2013
• The NIH Director’s Transformative Research Award (2018){{Cite web |last=Reuell |first=Peter |date=2018-10-31 |title=Seven Harvard researchers receive NIH funding for high-risk, high-reward research |url=https://news.harvard.edu/gazette/story/2018/10/seven-harvard-researchers-receive-nih-funding-for-high-risk-high-reward-research/?utm_source=chatgpt.com |access-date=2025-05-02 |website=Harvard Gazette |language=en-US}}
• The Breakthroughs in Gerontology (BIG) Award from the Glenn Foundation for Medical Research (2019){{Cite web |title=HSCI scientists receive “High-Risk, High-Reward” awards |url=https://www.hsci.harvard.edu/news/hsci-scientists-receive-high-risk-high-reward-awards?utm_source=chatgpt.com |access-date=2025-05-02 |website=www.hsci.harvard.edu |language=en}}

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Category:Living people

Category:1958 births

Category:French geneticists

Category:Developmental biologists

Category:University of Paris alumni

Category:Harvard Medical School faculty

Category:Members of the United States National Academy of Sciences