Worm Tracking

Worm tracking & analysis solution
MBF Bioscience > Worm Tracking

What is Worm Tracking?

Worm Tracking summarizes quantitative analysis of locomotion of worms. Most often, Worm Tracking refers to Caenorhabditis elegans (C. elegans) freely moving on agar plates and the specific behaviors underlying locomotion.

Fields Of Study

  • Neuroscience
  • Ageing
  • Genetics
  • Drug abuse and addiction
  • Toxicology
  • RNA interference and gene silencing
  • Sleep
  • Sensory biology

What is the significance of tracking freely moving C. elegans worms in modern neuroscience?

Defining the brain mechanisms underlying complex behaviors is the first goal in the Strategic Plan of the National Institute of Mental Health (NIMH) for Research [1]. Unfortunately, related mammalian models are often prohibitively expensive, time-consuming, and very complex. In this regard, it is noteworthy that the nematode C. elegans (one of the most versatile model organisms in modern biomedical research [2-4]) is increasingly used in research focusing on brain mechanisms underlying complex behaviors and pathological alterations thereof, including research into neurodevelopment [5, 6], Alzheimer’s disease [7, 8], autism [9, 10], schizophrenia [11, 12] and traumatic brain injury [13, 14]. This is due to the fact that C. elegans offers a number of unique advantages over other model organisms:

  • C. elegans has a short life span of approximately three to four weeks [13].
  • Maintenance and culturing of C. elegans is easy and inexpensive [15].
  • C. elegans‘ nervous system consists of 302 neurons, whose precise position, cell lineage, synaptic connectivity and wiring are known [18]. This provides a unique opportunity to understand how behavior emerges from activity in the nervous system of an organism [19].
  • The genome of C. elegans is fully sequenced [16].
  • Forward and reverse genetic approaches are available [17].
  • C. elegans express many of the neurotransmitters and associated receptors (including glutamate, GABA, acetylcholine, dopamine and serotonin [20]) that are found in higher eukaryotes, including humans. This makes C. elegans highly attractive for the (high throughput) screening of next generation therapeutics for mental diseases such as Alzheimer’s disease [21-23], as well as for disorders that rely on neurotransmitter release modulation, such as next generation treatments for schizophrenia [24].

In summary, C. elegans offers the promise of understanding the mechanisms underlying a whole animal’s behavior at the molecular and cellular levels [25, 26].

An article in the journal, The Scientist Magazine, pointed out that “Monitoring the worms’ neural activity while they roam freely to hunt food and seek mates is key, and fortunately, C. elegans are small and slow enough that microscopes can be built to track them as they move around.” [27].

 

Today, there are more than 1,100 laboratories worldwide that use C. elegans as a model organism [28].

 

When performed manually, worm tracking is not only very labor-intensive [29], but particularly prone to bias introduced by observer dependence [30]. For example, this has prevented manual quantitative analysis of locomotion of freely moving worms from being incorporated in medium-throughput toxicology assays [31]. To overcome this problem, several software or combined software/hardware products were developed with the aim to automatically detect and track freely moving worms with video microscopy systems.

What are WormLab and the WormLab Imaging System?

WormLab is a state-of-the-art software product for imaging, tracking, and analyzing C. elegans and other worms. It has a user-friendly software interface with a powerful, model-specific tracking algorithm that collects data about a single worm or multiple worms, even through omega bends, reversals and entanglements. The software analyzes virtually any video file type, including .avi, .wmv, and .mp4.

 

The WormLab Imaging System is a complete, scalable hardware solution for automated imaging and quantitative analysis of the behavior of C. elegans and other nematodes. MBF Bioscience worked closely with world leading C. elegans researchers to develop a unique worm tracking system that is intuitive and easy to use. For example, in conjunction with the WormLab software, the WormLab Imaging System enables researchers to correlate C. elegans locomotory behavior with the delivery of tapping or light stimuli.

 

WormLab was developed with support from NIEHS-SBIR grant ES017180.

How have WormLab and the WormLab Imaging System revolutionized worm tracking?

This has been achieved by:

 

  • a unique combination of specific worm tracking software and exactly matched microimaging hardware,
  • the implementation of an advanced, deformable shape estimation algorithm that is based on a model describing the worm’s shape and crawling motion, which is robust to coiling and entanglement [32, 33], and
  • the development of a turn-key solution consisting of WormLab software and the WormLab Imaging System that can be used by scientists without any expertise in developing software and microscope hardware.

WormLab and the WormLab Imaging System were used in numerous studies published in high-impact journals, including Cell [34], Cell Reports [35], Science Advances [36], eLife [37], Current Biology [38] and EMBO Reports [39], to mention only a few.

What kind of specific functionality is implemented in WormLab and the WormLab Imaging System?

WormLab and the WormLab Imaging System come with the following, specific functionality:

  • Automated detection of both head and body of single and multiple freely moving worms (resulting in unprecedented specificity and sensitivity in automated detection and tracking of C. elegans)
  • Automated tracking of multiple freely moving worms (allowing analysis of the interaction between multiple worms (such as mating behavior, etc.) with unprecedented validity and reliability)
  • Backtracking (i.e., interrupted track resolution by detection of a worm at a later time point and analyzing the position of the same worm backward through time to locate the source)
  • Support of different settings for magnification, image resolution, frame rate and the number of worms under study (resulting in fully flexible use of the WormLab Imaging System according to the user’s needs and special laboratory conditions)
  • Various illumination mode support (i.e., phase contrast and fluorescence illumination)
  • Multiple worm tracking with online (overlaid) display of the trajectories, morphological metrics and detected behavior patterns (phenotypic differences between different groups of worms (such as between mutant and wildtype worms, treated and untreated ones, etc.) reported as video sequences are acquired and analyzed)
  • Interactive tools for offline track processing (including a user-friendly feature for easily correcting tracking errors (such as track interruptions) resulting from conditions such as the occurrence of extreme worm entanglement, etc.)
  • Support of multi-well plates (which permits simultaneous analyses of multiple worms in successive multiple wells in medium- to high-throughput assays)
  • Integrated stimulus management by controlling a micromanipulator (facilitating observer-independence and high reliability in sophisticated, interactive behavioral assessments of freely moving worms such as chemical stimulation (drop tests).

Our Solution for Worm tracking

WormLab®

WormLab is a software for imaging, tracking, and analyzing C. elegans and other worms. It has a user-friendly software interface with a powerful model-specific tracking algorithm that collects data about a single worm or multiple worms, even through omega bends, reversals, and entanglements. The algorithm analyzes virtually any video file type, including .avi, .wmv, and .mp4.

It offers a wide variety of accurate analyses about a single or multiple worms, a user-friendly interface with a workflow, and comes with MBF’s technical and research support.

Use of WormLab in aging research: a success story

As animals and humans age, the motor system undergoes a progressive functional decline, leading to frailty. Age-dependent functional deterioration at neuromuscular junctions (NMJs) contribute to this motor aging. However, it is unclear whether one can intervene in this process to slow motor aging. The Caenorhabditis elegans BK channel SLO-1 dampens synaptic transmission at NMJs by repressing synaptic release from motor neurons. Here, we show that genetic ablation of SLO-1 not only reduces the rate of age-dependent motor activity decline to slow motor aging, but also surprisingly extends life span. SLO-1 acts in motor neurons to mediate both functions. Genetic knockdown or pharmacological inhibition of SLO-1 in aged, but not young, worms can slow motor aging and pro-long longevity. Our results demonstrate that genetic and pharmacological interventions in the aging motor nervous system can promote both health span and life span.

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References:

[1]     National Institute of Mental Health. Strategic Plan for Research. Available online at https://www.nimh.nih.gov/about/strategic-planning-reports (accessed on 19 October 2021).

[2]     Antoshechkin I, Sternberg PW. The versatile worm: genetic and genomic resources for Caenorhabditis elegans research. Nat Rev Genet 2007;8(7):518-532. doi: 10.1038/nrg2105.

[3]     Corsi AK, Wightman B, Chalfie M. A transparent window into biology: A primer on Caenorhabditis elegans. Genetics 2015;200(2):387-407. doi: 10.1534/genetics.115.176099.

[4]     Sterken MG, Snoek LB, Kammenga JE, Andersen EC. The laboratory domestication of Caenorhabditis elegans. Trends Genet. 2015;31(5):224-231. doi: 10.1016/j.tig.2015.02.009.

[5]     Cohn JA, Cebul ER, Valperga G, Brose L, de Bono M, Heiman MG, Pierce JT. Long-term activity drives dendritic branch elaboration of a C. elegans sensory neuron. Dev Biol 2020;461(1):66-74. doi: 10.1016/j.ydbio.2020.01.005.

[6]     Wirak GS, Gabel CV, Connor CW. Isoflurane exposure in juvenile Caenorhabditis elegans causes persistent changes in neuron dynamics. Anesthesiology 2020;133(3):569-582. doi: 10.1097/ALN.0000000000003335.

[7]     Benbow SJ, Strovas TJ, Darvas M, Saxton A, Kraemer BC. Synergistic toxicity between tau and amyloid drives neuronal dysfunction and neurodegeneration in transgenic C. elegans. Hum Mol Genet 2020;29(3):495-505. doi: 10.1093/hmg/ddz319.

[8]     Cogliati S, Clementi V, Francisco M, Crespo C, Argañaraz F, Grau R. Bacillus subtilis delays neurodegeneration and behavioral impairment in the Alzheimer’s disease model Caenorhabditis elegans. J Alzheimers Dis 2020;73(3):1035-1052. doi: 10.3233/JAD-190837.

[9]     Buddell T, Friedman V, Drozd CJ, Quinn CC. An autism-causing calcium channel variant functions with selective autophagy to alter axon targeting and behavior. PLoS Genet 2019;15(12):e1008488. doi: 10.1371/journal.pgen.1008488.

[10]   Wong WR, Brugman KI, Maher S, Oh JY, Howe K, Kato M, Sternberg PW. Autism-associated missense genetic variants impact locomotion and neurodevelopment in Caenorhabditis elegans. Hum Mol Genet 2019;28(13):2271-2281. doi: 10.1093/hmg/ddz051.

[11]   Dwyer DS, Awatramani P, Thakur R, Seeni R, Aamodt EJ. Social feeding in Caenorhabditis elegans is modulated by antipsychotic drugs and calmodulin and may serve as a protophenotype for asociality. Neuropharmacology 2015;92:56-62. doi: 10.1016/j.neuropharm.2014.12.027.

[12]   Monte GG, Nani JV, de Almeida Campos MR, Dal Mas C, Marins LAN, Martins LG, Tasic L, Mori MA, Hayashi MAF. Impact of nuclear distribution element genes in the typical and atypical antipsychotics effects on nematode Caenorhabditis elegans: Putative animal model for studying the pathways correlated to schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2019;92:19-30. doi: 10.1016/j.pnpbp.2018.12.010.

[13]   Angstman NB, Frank HG, Schmitz C. Hypothermia ameliorates blast-related lifespan reduction of C. elegans. Sci Rep 2018;8(1):10549. doi: 10.1038/s41598-018-28910-z.

[14]   Kunert JM, Maia PD, Kutz JN. Functionality and robustness of injured connectomic dynamics in C. elegans: linking behavioral deficits to neural circuit damage. PLoS Comput Biol 2017;13(1):e1005261. doi: 10.1371/journal.pcbi.1005261.

[15]   Avila D, Helmcke K, Aschner M. The Caenorhabiditis elegans model as a reliable tool in neurotoxicology. Hum Exp Toxicol 2012;31(3):236-243. doi: 10.1177/0960327110392084.

[16]   Gerstein MB, Lu ZJ, Van Nostrand EL, Cheng C, Arshinoff BI, Liu T, Yip KY, Robilotto R, Rechtsteiner A, Ikegami K, Alves P, Chateigner A, Perry M, Morris M, Auerbach RK, Feng X, Leng J, Vielle A, Niu W, Rhrissorrakrai K, Agarwal A, Alexander RP, Barber G, Brdlik CM, Brennan J, Brouillet JJ, Carr A, Cheung MS, Clawson H, Contrino S, Dannenberg LO, Dernburg AF, Desai A, Dick L, Dosé AC, Du J, Egelhofer T, Ercan S, Euskirchen G, Ewing B, Feingold EA, Gassmann R, Good PJ, Green P, Gullier F, Gutwein M, Guyer MS, Habegger L, Han T, Henikoff JG, Henz SR, Hinrichs A, Holster H, Hyman T, Iniguez AL, Janette J, Jensen M, Kato M, Kent WJ, Kephart E, Khivansara V, Khurana E, Kim JK, Kolasinska-Zwierz P, Lai EC, Latorre I, Leahey A, Lewis S, Lloyd P, Lochovsky L, Lowdon RF, Lubling Y, Lyne R, MacCoss M, Mackowiak SD, Mangone M, McKay S, Mecenas D, Merrihew G, Miller DM 3rd, Muroyama A, Murray JI, Ooi SL, Pham H, Phippen T, Preston EA, Rajewsky N, Rätsch G, Rosenbaum H, Rozowsky J, Rutherford K, Ruzanov P, Sarov M, Sasidharan R, Sboner A, Scheid P, Segal E, Shin H, Shou C, Slack FJ, Slightam C, Smith R, Spencer WC, Stinson EO, Taing S, Takasaki T, Vafeados D, Voronina K, Wang G, Washington NL, Whittle CM, Wu B, Yan KK, Zeller G, Zha Z, Zhong M, Zhou X; modENCODE Consortium, Ahringer J, Strome S, Gunsalus KC, Micklem G, Liu XS, Reinke V, Kim SK, Hillier LW, Henikoff S, Piano F, Snyder M, Stein L, Lieb JD, Waterston RH. Integrative analysis of the Caenorhabditis elegans genome by the modENCODE project. Science 2010;330(6012):1775-1787. doi: 10.1126/science.1196914.

[17]   Jorgensen EM, Mango SE. The art and design of genetic screens: caenorhabditis elegans. Nat Rev Genet 2002;3(5):356-369. doi: 10.1038/nrg794.

[18]   White JG, Southgate E, Thomson JN, Brenner S. The structure of the nervous system of the nematode Caenorhabditis elegans. Philos Trans R Soc Lond B Biol Sci 1986;314(1165):1-340. doi: 10.1098/rstb.1986.0056.

[19]   Chatterjee N, Sinha S. Understanding the mind of a worm: hierarchical network structure underlying nervous system function in C. elegans. Prog Brain Res 2008;168:145-153. doi: 10.1016/S0079-6123(07)68012-1.

[20]   Boyd WA, Smith MV, Kissling GE, Freedman JH. Medium- and high-throughput screening of neurotoxicants using C. elegans. Neurotoxicol Teratol 2010;32(1):68-73. doi: 10.1016/j.ntt.2008.12.004.

[21]   Griffin EF, Caldwell KA, Caldwell GA. Genetic and pharmacological discovery for Alzheimer’s disease using Caenorhabditis elegans. ACS Chem Neurosci 2017;8(12):2596-2606. doi: 10.1021/acschemneuro.7b00361.

[22]   Ma L, Zhao Y, Chen Y, Cheng B, Peng A, Huang K. Caenorhabditis elegans as a model system for target identification and drug screening against neurodegenerative diseases. Eur J Pharmacol 2018;819:169-180. doi: 10.1016/j.ejphar.2017.11.051.

[23]   Maglioni S, Arsalan N, Ventura N. C. elegans screening strategies to identify pro-longevity interventions. Mech Ageing Dev 2016;157:60-69. doi: 10.1016/j.mad.2016.07.010.

[24]   Dwyer DS. Crossing the worm-brain barrier by using Caenorhabditis elegans to explore fundamentals of human psychiatric illness. Mol Neuropsychiatry 2018;3(3):170-179. doi: 10.1159/000485423.

[25]   de Bono M, Maricq AV. Neuronal substrates of complex behaviors in C. elegans. Annu Rev Neurosci 2005;28:451-501. doi: 10.1146/annurev.neuro.27.070203.144259.

[26]   Schafer WR. Deciphering the neural and molecular mechanisms of C. elegans behavior. Curr Biol 2005;15(17):R723-R729. doi: 10.1016/j.cub.2005.08.020.

[27]   The Scientist Staff. Brains in action. Available at https://www.the-scientist.com/features/brains-in-action-38044 (accessed on 19 October 2021).

[28]   http://wbg.wormbook.org/the-worm-lab-project/all-labs/ (accessed on 19 October 2021).

[29]   Buckingham SD, Sattelle DB. Strategies for automated analysis of C. elegans locomotion. Invert Neurosci 2008;8(3):121-131. doi: 10.1007/s10158-008-0077-3.

[30]   Hart AC. Behavior. Available at http://wormbook.org/chapters/www_behavior/behavior.html (accessed on 19 October 2021).

[31]   Boyd WA, Smith MV, Kissling GE, Freedman JH. Medium- and high-throughput screening of neurotoxicants using C. elegans. Neurotoxicol Teratol 2010;32(1):68-73. coi: 10.1016/j.ntt.2008.12.004.

[32]   Roussel N, Morton CA, Finger FP, Roysam B. A computational model for C. elegans locomotory behavior: application to multiworm tracking. IEEE Trans Biomed Eng 2007;54(10):1786-1797. doi: 10.1109/TBME.2007.894981.

[33]   Roussel N, Sprenger J, Tappan SJ, Glaser JR. Robust tracking and quantification of C. elegans body shape and locomotion through coiling, entanglement, and omega bends. Worm 2015;3(4):e982437. doi: 10.4161/21624054.2014.982437.

[34]   Gong J, Yuan Y, Ward A, Kang L, Zhang B, Wu Z, Peng J, Feng Z, Liu J, Xu XZS. The C. elegans taste receptor homolog LITE-1 is a photoreceptor. Cell 2016;167(5):1252-1263.e10. doi: 10.1016/j.cell.2016.10.053.

[35]   Flores BN, Li X, Malik AM, Martinez J, Beg AA, Barmada SJ. An intramolecular salt bridge linking TDP43 RNA binding, protein stability, and TDP43-dependent neurodegeneration. Cell Rep 2019;27(4):1133-1150.e8. doi: 10.1016/j.celrep.2019.03.093.

[36]   Li G, Gong J, Liu J, Liu J, Li H, Hsu AL, Liu J, Xu XZS. Genetic and pharmacological interventions in the aging motor nervous system slow motor aging and extend life span in C. elegans. Sci Adv 2019;5(1):eaau5041. doi: 10.1126/sciadv.aau5041.

[37]   Hsueh YP, Gronquist MR, Schwarz EM, Nath RD, Lee CH, Gharib S, Schroeder FC, Sternberg PW. Nematophagous fungus Arthrobotrys oligospora mimics olfactory cues of sex and food to lure its nematode prey. Elife 2017;6:e20023. doi: 10.7554/eLife.20023.

[38]   Salzberg Y, Pechuk V, Gat A, Setty H, Sela S, Oren-Suissa M. Synaptic protein degradation controls sexually dimorphic circuits through regulation of DCC/UNC-40. Curr Biol 2020;30(21):4128-4141.e5. doi: 10.1016/j.cub.2020.08.002.

[39]   Turek M, Banasiak K, Piechota M, Shanmugam N, Macias M, Śliwińska MA, Niklewicz M, Kowalski K, Nowak N, Chacinska A, Pokrzywa W. Muscle-derived exophers promote reproductive fitness. EMBO Rep 2021;22(8):e52071. doi: 10.15252/embr.202052071.