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Associate Professor
The lab of Prof. Millet Treinin studies molecular determinants of neuronal function and dysfunction. We are currently studying: 1. Mechanisms enabling nicotine mediated protection of dopaminergic neurons, using C. elegans as a model system. 2. Mechanisms regulating synaptic efficacy and circuit activity in the C. elegans motor system focusing on cholinergic signaling. 3. The RIC-3 protein, an ER-resident chaperone of nicotinic acetylcholine receptors, and its roles in neuroinflammation.
Cell-specific gene expression analysis in Caenorhabditis elegans by targeted pull-down of messenger RNAs using an epitope tagged poly-A binding protein. This method will be used to examine effects of nicotine on gene expression in all neurons and specifically in dopaminergic neurons.
Conserved nicotine-activated neuroprotective pathways involve mitochondrial stress.
Nourse JB Jr, Harshefi G, Marom A, Karmi A, Cohen Ben-Ami H, Caldwell KA, Caldwell GA, Treinin M. iScience. 2021 Feb 4;24(3):102140. doi: 10.1016/j.isci.2021.102140. eCollection 2021 Mar 19. PMID: 33665559
In this research we describe a C. elegans model for nicotine-induced protection of dopaminergic neurons. Using this model we and our collaborators found that nicotine-induced protection involves mitochondrial stress and depends on PINK1 and Parkin, two proteins that are best known for their roles in activating mitophagy, thus promoting elimination of damaged mitochondria. These two proteins are also known for their role in Parkinson’s disease; loss of function mutations in the genes encoding for PINK1 and Parkin cause this disease. Together our results suggest a plausible explanation for epidemiological findings showing reduced prevalence of Parkinson’s disease among tobacco smokers.
RIC3, the cholinergic anti-inflammatory pathway, and neuroinflammation.
Ben-David Y, Kagan S, Cohen Ben-Ami H, Rostami J, Mizrahi T, Kulkarni AR, Thakur GA, Vaknin-Dembinsky A, Healy LM, Brenner T, Treinin M. Int Immunopharmacol. 2020 Jun;83:106381. doi: 10.1016/j.intimp.2020.106381. Epub 2020 Mar 14. PMID: 32179243
Genome wide association studies implicate ric3, encoding for a chaperone of nicotinic acetylcholine receptors (nAChRs), in multiple sclerosis (MS). In this research we examined the hypothesis that variants affecting expression of ric3 can affect activity of the cholinergic anti-inflammatory pathway and, therefore, contribute to MS progression. In support of this hypothesis we show that silencing of ric3interferes with the anti-inflammatory effects of cholinergic agonists. And, that altered expression of ric3 is found in activated immune cells and in some MS patients.
Safdie G, Liewald JF, Kagan S, Battat E, Gottschalk A, Treinin M. Mol Biol Cell. 2016 Oct 1;27(19):2994-3003. doi: 10.1091/mbc.E16-05-0265. Epub 2016 Aug 3. PMID: 27489343
This research describes a homeostatic mechanism enabling regulation of excitation-inhibition balance in C. elegans. Specifically we have shown that phosphorylation of RIC-3 leads to reduced inhibitory drive via reduced functional expression of GABAA receptors. Our results suggest that in response to increased excitation Calcineurin, a calcium and calmodulin dependent phosphatase, dephosphorylates RIC-3 to increase inhibition; thus restoring excitation to inhibition balance.
Caenorhabditis elegans nicotinic acetylcholine receptors are required for nociception.
Cohen E, Chatzigeorgiou M, Husson SJ, Steuer-Costa W, Gottschalk A, Schafer WR, Treinin M. Mol Cell Neurosci. 2014 Mar;59:85-96. doi: 10.1016/j.mcn.2014.02.001. Epub 2014 Feb 8. PMID: 24518198
This research examined the functions of nAChRs in C. elegans nociceptors. Our results demonstrate a central role for nAChRs in C. elegans nociception. Classic experiments have shown that application of acetylcholine to skin burns causes pain. Our work suggests that this acetylcholine-induced pain can be explained by activation of nociceptor-expressed nAChRs that, in mammals like C. elegans, activate nociceptor signaling.
The C. elegans ric-3 gene is required for maturation of nicotinic acetylcholine receptors.
Halevi S, McKay J, Palfreyman M, Yassin L, Eshel M, Jorgensen E, Treinin M. EMBO J. 2002 Mar 1;21(5):1012-20. doi: 10.1093/emboj/21.5.1012. PMID: 11867529
This paper describes the cloning and characterization of RIC-3; an ER-resident chaperone of nAChRs. C. elegans RIC-3 is the first representative of a conserved family of nAChR chaperones. This research shows that in C. elegans RIC-3 promotes functional expression of multiple nAChR. Later studies demonstrated a similar function of mammalian RIC-3 homologs.
Cholinergic transmission in C. elegans: Functions, diversity, and maturation of ACh-activated ion channels.
Treinin M, Jin Y. J Neurochem. 2021 Sep;158(6):1274-1291. doi: 10.1111/jnc.15164. Epub 2020 Sep 25. PMID: 32869293
This review summarizes research on cholinergic transmission in C. elegans focusing on the large and diverse family of C. elegans nAChRs, their properties, functions, and the mechanisms regulating their maturation.
Lab manager
Cell-specific gene expression analysis in Caenorhabditis elegans by targeted pull-down of messenger RNAs using an epitope tagged poly-A binding protein. This method will be used to examine effects of nicotine on gene expression in all neurons and specifically in dopaminergic neurons.
We are looking for highly motivated postdoc and student to join the lab.
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1981-1984 BSc in Biology, Hebrew University
1984-1986 MSc in Biology, Weizmann Institute; 1992- PhD in Genetics, Hebrew University 1992-1995 Post-doctoral fellow, Columbia University, NY
199-2003 Lecturer, Hadassah Medical School, Hebrew University
2003-2011 Senior Lecturer
2011 – Associate Professor
responsibilities include:
96201 – Introduction of cellular physiology
96207 – The nervous system of the healthy person (the physiology part)