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Neurons, synapses, and the proteins required for their function are critical to the biology and behaviour of animals, but little is known about how they first evolved. In neurons, the transmission of chemical signals (called neuropeptides or neurotransmitters) from the presynapse to the postsynapse requires distinct sets of pre- and postsynaptic protein networks. Understanding when the proteins required for synaptic activity first evolved and how they functioned in the first animals promises to illuminate evolutionary processes underlying the origin of neurons. We are particularly interested in:
- The origin and functional evolution of synaptic proteins
- Co-option of these proteins into ancient synaptic scaffolds
- Evolution of the first neuron-like cell type in animals
We use a comparative approach and work with choanoflagellates, the closest unicellular relatives of animals, sponges, early branching animals with no synapses and neurons, and ctenophores, early branching animals with synapses and neurons, as model organisms. We aim to understand when the proteins required for synaptic activity first evolved, how they functioned at a molecular level and which combinations of synaptic proteins resulted in the origin of the synapse. Our approach is to use a variety of techniques, ranging from comparative genomics, immunofluorescence and electron microscopy, current state-of-the-art biochemical methods to X-ray crystallography to study synaptic protein homologs in choanoflagellates, sponges and ctenophores. Through our work we will be able to reconstruct the evolutionary history of these proteins and understand the evolution of the first synapses and neurons.
Gahan JM, Kouzel IU, Jansen KO, Burkhardt P, Rentzsch F (2022) Histone demethylase Lsd1 is required for the differentiation of neural cells in Nematostella vectensis. Nature Communications 13 (1):465.
Sachkova MY, Eva-Lena Nordmann EL, Soto Angel JJ, Yasmin Meeda Y, Górski B, Naumann B, Dondorp D, Chatzigeorgiou M, Kittelmann M, Burkhardt, P (2021) Neuropeptide repertoire and 3D anatomy of the ctenophore nervous system. Current Biology 31, 5274–5285. (preprint avialable here bioRxiv).
Burkhardt P and Jékely G (2021) Evolution of Synapses and Neurotransmitter Systems: The Divide-and-Conquer Model for Early Neural Cell-Type Evolution. Current Opinion in Neurobiology (71) 127-138. (preprint available here Preprints).
Musser JM, Schippers KJ, Nickel M, Mizzon G, Kohn AB , Pape C, Hammel JU, Wolf F, Liang C, Hernández-Plaza A, Achim K, Schieber NL, Francis WR, Vargas S, Kling S, Renkert M, Feuda R, Gaspar I, Burkhardt P, Bork P, Beck M, Kreshuk A, Wörheide G, Huerta-Cepas J, Schwab Y, Moroz LL, Arendt D (2021) Profiling cellular diversity in sponges informs animal cell type and nervous system evolution. Science 374 (6568), 717-723. (preprint avialable here bioRxiv).
Hake KH, West PT, McDonald K, Laundon D, Feng C, Burkhardt P, Richter D, Banfield JF, King N. (2021) Colonial choanoflagellate isolated from Mono Lake harbors a microbiome. bioRxiv 437421.
Goehde RA*, Naumann B*, Laundon D, Imig C, McDonald K, Cooper BH, Varoqueaux F, Fasshauer D, Burkhardt P (2021) Choanoflagellates and the ancestry of neurosecretory vesicles. Phil. Trans. R. Soc. B 376: 20190759. (*joint 1st author). (preprint avialable here bioRxiv).
Nauman B, Burkhardt P (2019) Spatial cell disparity in the colonial choanoflagellate Salpingoeca rosetta. Frontiers in Cell and Developmental Biology 7 (231). (preprint avialable here bioRxiv).
Sachkova M, Burkhardt P (2019) Exciting times to study the identity and evolution of cell types. Development 146: dev178996.
Laundon D, Larson B, McDonald K, King N, Burkhardt P (2019) The architecture of cell differentiation in choanoflagellates and sponge choanocytes. PLoS Biology 17 (4): e3000226. (recommended by F1000) (preprint avialable here bioRxiv).
Kollmar M, Welz T, Straub F, Alzahofi N, Hatje K, Briggs DA, Samol-Wolf A, Burkhardt P, Hume A, Kerkhoff E (2019) Animal evolution coincides with a novel degree of freedom in exocytic transport processes. bioRxiv 452185.
- Morey C, Kienle CN, Klöpper TH, Burkhardt P, Fasshauer D (2017) Evidence for a conserved inhibitory binding mode between the membrane fusion assembly factors Munc18 and syntaxin in animals. Journal of Biological Chemistry 292 (50): 20449-20460.
- Burkhardt P, Sprecher SG (2017) Evolutionary origin of synapses and neurons – Bridging the gap. BioEssays 39 (10): 1700024.
- Hoffmeyer TT and Burkhardt P (2016) Choanoflagellate models – Monosiga brevicollis and Salpingoeca rosetta. Current Opinion in Genetics and Development (39) 42-47.
- Bhattacharyya M*, Stratton MM*, Going CC*, McSpadden E, Huang Y, Susa AC, Elleman A, Cao YM, Pappireddi N, Burkhardt P, Gee C, Barros T, Schulman H, Williams ER, Kuriyan J (2016) Molecular mechanism of activation-triggered subunit exchange in Ca2+/calmodulin-dependent protein kinase II. Elife 5: e13405. (*joint 1stauthor).
- Burkhardt P (2015) The origin and evolution of synaptic proteins – choanoflagellates lead the way. Journal of Experimental Biology (218): 506-514.
- Burkhardt P, Gronborg M, McDonald K, Sulur T, Wang Q, King N (2014) Evolutionary insights into premetazoan functions of the neuronal protein Homer. Molecular Biology and Evolution 31 (9): 2342–2355.
- Demircioglu FD, Burkhardt P, Fasshauer D (2014) The SM protein Sly1 accelerates assembly of the ER-Golgi SNARE complex. Proceedings of the National Academy of Sciences 111 (38): 13828-13833.
- Sebe-Pedros A*, Burkhardt P*, Sánchez-Pons N, Fairclough SR, Lang F, King N, Ruiz- Trillo I (2013) Insights into the origin of metazoan filopodia and microvilli. Molecular Biology and Evolution 30 (9): 2013-2023 (*joint 1st author).
- Colbert KN, Hattendorf DA, Weiss TM, Burkhardt P, Fasshauer D, Weis WI (2013) Syntaxin1a variants lacking an N-peptide or bearing the LE mutation bind to Munc18a in a closed conformation. Proceedings of the National Academy of Sciences, 110 (31): 12637-42.
- Meijer M*, Burkhardt P*, de Wit H, Toonen RF, Fasshauer D, Verhage M (2012) Munc18-1 mutations that strongly impair SNARE-complex binding support normal synaptic transmission. EMBO Journal 31 (9): 2156-2168 (*joint 1st author). (recommended by F1000)
- Burkhardt P, Stegmann CM, Cooper B, Kloepper TH, Imig C, Varoqueaux F, Wahl MC, Fasshauer D (2011) Primordial neurosecretory apparatus identified in the choanoflagellate Monosiga brevicollis. Proceedings of the National Academy of Sciences, 108 (37): 15264-15269.
- Burkhardt P, Hattendorf DA, Weis WI, Fasshauer D (2008) Munc18 controls SNARE assembly through its interaction with the syntaxin N-peptide. EMBO Journal 27 (7): 923-933.(recommended by F1000)
- (2022). Histone demethylase Lsd1 is required for the differentiation of neural cells in Nematostella vectensis. Nature Communications.
- (2021). Profiling cellular diversity in sponges informs animal cell type and nervous system evolution. Science. 717-723.
- (2021). Neuropeptide repertoire and 3D anatomy of the ctenophore nervous system. Current Biology. 5274-5285.e6.
- (2021). Choanoflagellates and the ancestry of neurosecretory vesicles. Philosophical Transactions of the Royal Society of London. Biological Sciences. 1-12.
- (2019). The architecture of cell differentiation in choanoflagellates and sponge choanocytes. PLoS Biology. 1-22.
- (2019). Spatial cell disparity in the colonial choanoflagellate salpingoeca rosetta. Frontiers in Cell and Developmental Biology. 1-19.
- (2021). Evolution of synapses and neurotransmitter systems: The divide-and-conquer model for early neural cell-type evolution. Current Opinion in Neurobiology. 127-138.
- (2019). Exciting times to study the identity and evolution of cell types. Development. 1-6.
Pawel Burkhardt is a research group leader at the Sars International Centre for Marine Molecular Biology in Bergen, Norway. His research has the primary focus on using marine organisms to understand the molecular and cellular mechanisms that underlie the origin of synapses and neurons. He studied Biology at the University of Göttingen, Germany and Manchester, UK and joined the lab of Dirk Fasshauer at the Max-Planck-Institute for Biophysical Chemistry, Germany for his Master's thesis and PhD, where he worked on rat and choanoflagellate (neuro-) secretory proteins (Burkhardt et al, 2008 EMBO J; Burkhardt et al, 2011 PNAS; Meijer*, Burkhardt et al, 2012 EMBO J). For his postdoc he studied choanoflagellate postsynaptic protein homologs, in the lab of Nicole King at the University of California, Berkeley, USA (Burkhardt et al, 2014 MBE; Bhattacharyya et al, 2016 eLife). Prior to starting his research group "Evolutionary Origin of Synapses and Neurons" at the Sars Centre in 2018 he worked as a Research Fellow at the Marine Biological Association, UK. He was awarded the Anne Warner endowed Fellowship in 2014, the Royal Society University Research Fellowship in 2017 and an ERC consolidator grant in 2022.