Paul H. Taghert, Ph.D.

Professor
Neuroscience

Neurosciences Program
Developmental, Regenerative and Stem Cell Biology Program

  • 314-660-1527

  • 314-362-3645

  • 314 660-1527

  • 314-362-3446

  • 8108

  • 469 McDonnell Medical Sciences Building

  • taghertp@wustl.edu

  • https://sites.wustl.edu/taghertlab/

  • circadian rhythm, neuropeptide, GPCR, 2nd messengers, Drosophila

  • Circadian physiology and behavior

Research Abstract:

My laboratory studies circadian neurophysiology using the model system Drosophila. We ask how circadian timing information is used by dedicated pacemaking neural circuits to regulate daily behavior. In Drosophila, the pacemaker circuit consists of ~150 neuronal pacemakers that have special dedication to circadian timekeeping and control daily rhythmic behaviors. To learn about the patterns of pacemaker activity, we measured calcium levels across the entire network, brain-wide and in vivo over 24 hr, in collaboration with Tim Holy (Neuroscience, WUMS). We found that different pacemaker groups are sequentially active at precise times of day. In so doing circadian neuronal output divides the 24 hr day: this series of sequential activity phases includes a Morning one, a Mid-Day one, an Evening one and two that divide the Night. These distinct temporal outputs are aligned with downstream neurons that control different physiological functions, (e.g., feeding, sleeping, locomotion, reproduction). Currently we pursue two main research questions using imaging, genetics, biochemistry and behavioral analysis.

The first asks how a set of pacemakers decode their synchronous intrinsic circadian timing into a staggered pattern of neuronal activation. Based on genetics and physiology, our working hypothesis is that all pacemakers in this circuit are Morning Cells, according to their intrinsic clock, but only some are permitted that phase. All others are differentially delayed by many hours via neuropeptide-mediated suppression of their activity periods. We therefore study the signaling details by which neuropeptides (like PDF) ,secreted by different pacemakers, regulate calcium mobilization and thus activity periods in target pacemakers.

The second question concerns the receptor for PDF: it is a GPCR, which, in addition to regulating Calcium mobilization, also synchronizes the 24 h molecular clock across pacemakers. We have used CRISPR methods to create Drosophila lines with fluorescent proteins attached to the ends of the endogenous PDF GPCR. We now use these to study the distributions and dynamics of the PDF-R in live brains. We also study the receptor by combining our lines with ones in which endogenous clock proteins (like PER and CRY) are also labeled by fluorescence. Here we seek to learn about the mechanisms of PDF-R-mediated clock synchronization.



Mentorship and Commitment to Diversity Statement:
I enjoy mentoring trainees and benefit personally by learning with and from them. I work to ensure consistent communications and clear expectations with mentees. I seek to instill pride by mentees not just in scientific experimentation, but also in scientific communication. I promote the value of co-mentoring and peer-peer mentoring. I work to be mindful of my mentoring approach and how it can improve. Within my laboratory and across the School, I work to promote greater inclusion and a supportive environment for trainees and faculty from groups currently under-represented in the Sciences. This aim requires concerted and sustained efforts to change the academic culture and so strengthen our Institution.

Selected Publications:


Liang X., Holy, T.E., Taghert, P.H. (2022) The Drosophila circadian pacemaker circuit is a polyphasic rhythm generator.
Biorxiv.org/content/10.1101/2022.10.11.511837v1

Liang X, Holy TE, Taghert PH. (2022) Circadian pacemaker neurons display co-phasic rhythms in basal calcium level and in fast calcium fluctuations. Proc Nat. Acad Sci; DOI: 10.1073/pnas.2109969119.

Li, W, Trigg JS, Taghert PH.(2022) Regulation of PDF Receptor Signaling Controlling Daily Locomotor Rhythms in Drosophila. PLoS Genetics; 18(5):e1010013. PMID: 35605015; PMCID: PMC9166358.

Taghert PH (2022) The incidence of candidate binding sites for beta-arrestin in Drosophila neuropeptide GPCRs. PLoS ONE Nov 1; doi.org/10.1371/journal.pone.0275410.

Liang X, Ho CW, Zhang Y, Li Y, Wu MN, Holy TE, Taghert PH. Morning and Evening Circadian Pacemakers Independently Drive Premotor Centers via a Specific Dopamine Relay. Neuron. 2019; 102(4):843-57. e4. PMID: 3098153.

Liang, X.. Holy T.E. & Taghert, P.H. (2017) A Series of Suppressive Signals within the Drosophila Circadian Neural Circuit Generates Sequential Daily Outputs. Neuron. June 21; 94(6): 1173-1189. PMID: 28552314.

Klose, M., Duvall, L.B., Li, W., Liang, X., Ren, C., Steinbach, J.H., & Taghert, P.H. (2016) Functional Pdf Signaling In the Drosophila Circadian Neural Circuit Is Gated by Ral A-Dependent Modulation. Neuron May 18;90(4):781-794. PMID: 27161526

Liang, X., Holy, T.E., & Taghert, P.H. (2016) Synchronous Drosophila circadian pacemakers display non-synchronous Ca2+ rhythms in vivo. Science (Wash.), 351: 976-981. PMID: 26917772

Duvall, L.B. & Taghert, P.H. (2012) The circadian neuropeptide PDF signals preferentially through a specific adenylate cyclase isoform AC3 in M pacemakers of Drosophila. PLoS Biology 10(6): e1001337. PMID: 22679392

Shafer, O.T., Kim, D.J., Nikolaev, V., Dunbar-Jaffe, R., Lohse, M. & Taghert, P.H. (2008) Widespread receptivity to neuropeptide PDF throughout the neuronal circadian clock network of Drosophila revealed by real-time cyclic AMP imaging. Neuron 58: 223-237. PMID: 18439407

Martens, I., Vandingenen, A., Johnson, E.C., Shafer, O.T., Li, W., Trigg, J.S., De Loof, A., Schools, L. & Taghert, P.H. (2005) PDF receptor signaling in Drosophila contributes to both circadian and geotactic behaviors. Neuron 48: 213-219. PMID: 16242402

Lin, Y., Stormo, G.D., & Taghert, P.H. (2004) The neuropeptide pigment-dispersing factor coordinates pacemaker interactions in the Drosophila circadian system. J Neurosci. 24:7951-7. PMID: 15356209

Lin, Y., Han, M., Shimada, B., Wang, L., Gibler, T.M., Amaorone, A., Awad, T., Stormo, G.D., Van Gelder, R.N., & Taghert, P.H. (2002) Influence of the period-dependent circadian clock on diurnal, circadian, and aperiodic gene expression in Drosophila melanogaster. Proc. Nat. Acad. Sci, USA 99:9562-9567. PMID: 12089325

Renn, S.C.P., Park, J., Rosebash, M., Hall, J.C. & Taghert, P.H. (1999) A pdf neuropeptide gene mutation and ablation of PDF-containing neurons each cause severe abnormalities of circadian behavioral rhythms in Drosophila. Cell, 99:791-802. PMID: 10619432

Last Updated: 11/8/2022 9:48:04 AM

Imaging the fly brain in vivo in realtime
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