Paul H. Taghert

Taghert was born on January 13, 1953, in Alexandria, Egypt and grew up in Montclair, New Jersey. He attended Reed College from 1971 to 1975 and went on to pursue a PhD in zoology at the University of Washington in Seattle with Jim Truman. He did a postdoc under Corey Goodman at Stanford University from 1981 to 1984. As of 2016, he is a professor of neuroscience at Washington University in St. Louis and the Lab Head at the Taghert Lab at Washington University School of Medicine.

Taghert and colleagues have identified the ~150 circadian clock neurons in the adult Drosophila melanogaster brain.{{Cite journal|title = Setting the clock – by nature: Circadian rhythm in the fruitfly Drosophila melanogaster|last = Peschel|first = Nicolai|date = May 20, 2011|journal = FEBS Letters|doi = 10.1016/j.febslet.2011.02.028|pmid = 21354415|volume=585|issue = 10|pages=1435–1442|doi-access = free}} Two distinct regions, the small and large ventral lateral neurons (LNv), express the neuropeptide pigment dispersing factor (PDF) and contribute to circadian locomotor activity rhythms.{{cite journal|last1=Stoleru|first1=Dan|last2=Peng|first2=Ying|last3=Agosto|first3=José|last4=Rosbash|first4=Michael|title=Coupled oscillators control morning and evening locomotor behavior of Drosophila|journal=Nature|date=14 October 2004|volume=431|issue=7010|pages=862–868|doi=10.1038/nature02926|pmid=15483615|bibcode=2004Natur.431..862S |s2cid=4394441}} Taghert's group has made several contributions including the identification of mutants for the PDF neuropeptide gene - this revealed a specific behavioral syndrome indicating important contributions by this neuropeptide to normal circadian control of locomotor activity. This was the first genetic study identifying secreted substances (and not just clock elements) as critical proteins for circadian neurophysiology. This led the way to many studies by many laboratories that now evaluate how neuronal properties interweave and interact with cell intrinsic clock properties.

Taghert's work involves employing the GAL4 activation and GAL80 inhibition of PDF to study PDF's necessity as a circadian pacemaker. Experiments with the LNvs found that ablation of PDF via GAL80 inhibition only affected some aspects of behavioral rhythms, suggesting the presence of other regulators controlling circadian behavior. To further examine the peptidergic pathways regulating PDF, Taghert and his group discovered the PDF receptor (PDFR), a class B1 G protein coupled receptor. Null mutations of PDFR suggests that it is also required for circadian rhythms in Drosophila melanogaster.{{cite journal|last1=Kunst|first1=Michael|last2=Tso|first2=Matthew C.F.|last3=Ghosh|first3=D. Dipon|last4=Herzog|first4=Erik D.|last5=Nitabach|first5=Michael N.|title=Rhythmic control of activity and sleep by class B1 GPCRs|journal=Critical Reviews in Biochemistry and Molecular Biology|date=5 November 2014|volume=50|issue=1|pages=18–30|doi=10.3109/10409238.2014.985815|pmid=25410535|pmc=4648372}}

The Taghert group also demonstrated that PDF signaling influences pacemaker cell synchronicity through PER regulation, identified the PDF receptor, and identified critical PDF receptor signaling components.{{cite journal|last1 = Herzog|first1 = Erik D.|title = Neurons and networks in daily rhythms|journal = Nature Reviews Neuroscience|date = October 2007|volume = 8|issue = 10|pages = 790–802|doi = 10.1038/nrn2215|pmid=17882255|s2cid = 33687097}} They have shown that PDF receptor signals differently in different pacemaker groups, and that PDF receptor signaling interact with signals from Cryptochrome (CRY) to help sustain clock rhythmicity.{{cite journal|last1 = Li|first1 = Yue|last2 = Guo|first2 = Fang|last3 = Shen|first3 = James|last4 = Rosbash|first4 = Michael|title = PDF and cAMP enhance PER stability in Drosophila clock neurons|journal = Proceedings of the National Academy of Sciences of the United States of America|date = February 11, 2014|volume = 111|issue = 13|doi = 10.1073/pnas.1402562111|pmid=24707054|pmc=3977231|pages=E1284–E1290| bibcode=2014PNAS..111E1284L |doi-access = free}}

Taghert's work on DIMM addresses the genetic programs underlying neuron diversification.{{cite journal|last1=Dongkook|first1=Park|last2=Veenstra|first2=Jan|last3=Park|first3=Jae|last4=Taghert|first4=Paul|title=Mapping Peptidergic Cells in Drosophila: Where DIMM Fits In|journal=PLOS ONE|date=March 26, 2008|volume=3|issue=3|doi=10.1371/journal.pone.0001896|pmid=18365028|pmc=2266995|pages=e1896|bibcode=2008PLoSO...3.1896P |doi-access=free}} Through a developmental studies approach, his work explores how peptidergic neurons in Drosophila use transcriptional control mechanisms to acquire properties like the selection of a unique neuropeptide phenotype.{{cite journal|last1=Nassel|first1=Dick R.|title=Drosophila neuropeptides in regulation of physiology and behavior|journal=Progress in Neurobiology|date=September 2010|volume=92|issue=1|doi=10.1016/j.pneurobio.2010.04.010|pmid=20447440|pages=42–104|s2cid=24350305}} The bHLH protein DIMM is an example of a transcriptional control mechanism that operates in neurosecretory neurons and is responsible for the cells’ ability to accumulate, process, and package large amounts of secretory peptides.

DIMM confers a specific peptidergic phenotype to neurons, referred to as LEAP cells (Large cells that Episodically release Amidated Peptides). To map DIMM expression in Drosophila peptidergic systems, a large panel of peptide antibodies and gene reporters were used. It was found that there is a substantial correlation of DIMM expression with peptidergic phenotypes. At a molecular level, DIMM concerns secretory peptides that are amidated, and at a cellular level, DIMM concerns peptidergic neurons which are neurosecretory. Current research involves molecular pathways by which DIMM levels are induced in response to environmental challenges.{{cite web|title=Paul Taghert|url=http://dbbs.wustl.edu/faculty/Pages/faculty_bio.aspx?SID=1534|website=Washington University in St. Louis Division of Biology & Biomedical Sciences}}

• {{cite journal|last1=Renn |first1=S.C.P. |first2=Park |last2=J.H. |first3=M. |last3=Rosbash |first4=J.C. |last4=Hall |first5=P.H. |last5=Taghert |year=1999 |title=A pdfNeuropeptide Gene Mutation and Ablation of PDF Neurons Each Cause Severe Abnormalities of Behavioral Circadian Rhythms in Drosophila |journal=Science |pages=781–802 |doi=10.1016/S0092-8674(00)81676-1 |volume=99 |issue=7 |pmid=10619432|doi-access=free }}
• {{cite journal|last1=Mertens |first1=Inge |first2=Anick |last2=Vandingenen |first3=Eric C. |last3=Johnson |first4=Orie |last4=Shafer |first5=W. |last5=Li |first6=J.S. |last6=Trigg |first7=Arnold |last7=De Loof |first8=Liliane |last8=Schoofs |first9=Paul |last9=Taghert |year=2005 |title=PDF Receptor Signaling in Drosophila Contributes to Both Circadian and Biotactic Behaviors |journal=Neuron |issue=2 |pages= 213–219 |doi=10.1016/j.neuron.2005.09.009 |volume=48 |pmid=16242402|doi-access=free }}

{{Reflist}}

• [http://dbbs.wustl.edu/faculty/Pages/faculty_bio.aspx?SID=1534 Washington University in St. Louis Faculty Bio]
• [https://hopecenter.wustl.edu/?faculty=paul-taghert-phd Hope Center at WUSTL]

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Category:1953 births

Category:Living people

Category:American microbiologists

Category:American chronobiologists

Category:Reed College alumni

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Category:Stanford University fellows

Category:Washington University School of Medicine faculty