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    Mark Alkema PhD

    TitleAssistant Professor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentNeurobiology
    AddressUniversity of Massachusetts Medical School
    364 Plantation Street, LRB
    Worcester MA 01605
    Phone508-856-6158
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentNeuroscience

        Overview 
        Narrative

        Biography

        Mark Alkema received his B. Sc. (1990) from the University of Amsterdam and Ph.D. (1996) from the Netherlands Cancer Institute in Amsterdam. He received a Human Frontiers Science Program fellowship and a Merck / M.I.T. Fellowship to do postdoctoral work at the Massachusetts Institute of Technology in the laboratory of Bob Horvitz. He joined the Department of Neurobiology at the University of Massachusetts Medical School as a faculty member in June, 2005.

        C. elegans Behavioral Genetics

        University of Massachusetts Medical School UMass Mark Alkema, Ph.D. Our focus is to understand the molecular and cellular basis of behavioral plasticity. We are studying how the environment modulates behavior of the nematode Caenorhabditis elegans. The C. elegans nervous system is very simple and extraordinarily well described. The detailed knowledge  of the C. elegans nervous system combined with its amenability to genetic analysis and laser microsurgery allows us to define neural circuits that control behavior and study behavior at the molecular and cellular level.

        How does the nervous system translate sensory information into behavioral response? Facing the complexity of the mammalian nervous system this fundamental question presents daunting task. Some of the rare cases where we actually know the neural path, from sensory input to motor output, have come from the analyses of escape responses in mollusks, crayfish and goldfish (Korn and Faber, 2005; Edwards et al., 2002; Allen et al., 2006). Defining sensorimotor circuits requires detailed knowledge of the neural connectivity of the nervous system, and the ability to manipulate the functions of the component neurons and to define and quantify the behavioral outputs. The simplicity and completely defined synaptic connectivity of C. elegans nervous system provides unique opportunity to dissect how neural networks control behavior. Moreover, the combination of powerful genetic methods, calcium imaging and electrophysiology allows us to address how the nervous controls behavior with a cellular and molecular resolution that cannot be readily attained in other systems.

        C. elegans escape responseGentle touch elicits an escape response C. elegans where the animal displays characteristic sequence of behaviors to get away from the stimulus. C. elegans moves on its side by propagating a sinusoidal wave of body wall muscle contractions along the length of its body. C. elegans locomotion is accompanied by oscillatory head movements during which the tip of the nose moves rapidly from side to side. First, in response to touch to the anterior half of the body of the animal reverses its direction of locomotion (Chalfie et al., 1985). During this reversal the animals suppresses its lateral head movements (Alkema et al., 2005). Second, the reversal is followed by a deep ventral head bend. Third, the animal makes a sharp turn where it slides the head down the ventral side of the body. This sharp turn (Omega turn) results in approximately 180° change in locomotion anterior. Fourth, the animal resumes forward locomotion and exploratory head movements. Based on the strength of the stimulus the animal has to decide whether to engage in an escape response. Once it does, the animal needs coordinate distinct motor programs, generate asymmetry in its locomotion pattern to allow it to make a sharp turn before it returns to a base state. Our goal is to elucidate what neurons, neurotransmitters and receptors define neural circuits that control these motor programs, and how these motor programs are linked temporally in the execution of the worm escape response.

        C. elegans escape response neural circuitOur previous work and that of others has provided some clues about the neurons that are required for these motor programs. The C. elegans neural wiring diagram and laser ablation experiments support a model in which the touch sensory neurons inhibit the forward locomotion command neurons and activate the backward command neurons causing the animal to move backward away from the stimulus. We have shown that the trace amine, tyramine, plays a crucial role in the coordination of the backing response and the suppression of head oscillations in the escape response. A pair of tyraminergic motorneurons is activated through gap junctions with the backward locomotion command neurons, triggering the release of tyramine (Alkema et al., 2005). Tyramine coordinates two motor programs by inhibiting the forward locomotion command neurons and directly hyperpolarizing neck muscles through the activation of a novel tyramine gated chloride channel, LGC-55 (Pirri et al., 2009).

        In predator-prey experiments we have been able to show that the suppression of head movements allows the animal to escape from nematophagous fungi that entrap nematodes. Tyramine signaling mutants that fail to suppress head oscillations on response to touch are more likely to get caught in constricting hyphal rings that inflate upon contact (Maguire et al., 2011). Which neurons are required for the steep ventral head bend, and how the motor neurons in the ventral cord execute an omega turn is largely unknown. Moreover, it is not clear how a long reversal is coupled to an omega turn.

        C. elegans caught by the nematophagous fungus, Drechslerella doedycoidesWhile we have shown that a fast acting ionotropic tyramine receptors is involved in the immediate suppression of head oscillations and reversal upon touch, the slower acting metabotropic tyramine receptors appear to be involved in the execution of the omega turn. We found that the G-protein coupled tyramine receptor, SER-2, is expressed in a subset of inhibitory GABAergic neurons that innervate body wall muscles on the ventral side of the animal. Our genetic and behavioral analyses indicate that SER-2 inhibits GABA release to allow the animal to hypercontract its ventral side during the execution of an omega turn. ser-2 mutants initiate a normal escape response but fail to touch head to tail during an omega turn. This suggests that aminergic modulation of ventral cord motorneurons may allow the animal to generate asymmetry in its locomotion pattern (Donnelly et al., 2013).

        Ultimately, we hope that our studies will teach us more about the basic principles that underlie behavioral plasticity of more complex neural systems.

        Featured Articles
      • UMass Medical School receives Gates Foundation grant for groundbreaking research in global health and development
      • Is This Virtual Worm the First Sign of the Singularity?
      • How the Worm Turns, in Molecular Detail
      • How a Neurotransmitter Acts to Coordinate a Compound Movement Through Two Different Receptors in C. Elegans
      • Scientists study evolutionary arms race in worms
      • Elusive Prey: Selection Pressures Imposed by Predator Fungi Have Shaped Escape Behavior in Microscopic Worms
      • UMMS Scientists Receive Gates Foundation Grand Challenges Exploration Grant
      • Video - C. elegans caught by the nematophagous fungus, Drechslerella doedycoidesVIDEO: C. elegans caught by nematophagous fungus
        Video - Invertebrate Research at UMass Medical SchoolVIDEO: Invertebrate Research at UMass Medical School



        Personnel

        University of Massachusetts Medical School UMass Jennifer PirriJennifer Pirri Ph.D.
        Postdoctoral Fellow
        jennifer.pirri@umassmed.edu

        University of Massachusetts Medical School UMass Christopher ClarkChristopher Clark
        Graduate Student
        christopher.clark@umassmed.edu

        University of Massachusetts Medical School UMass Yung-Chi HuangYung-Chi Huang
        Graduate Student
        yung-chi.huang@umassmed.edu

        University of Massachusetts Medical School UMass Jeremy FlormanJeremy Florman
        Graduate Student
        jeremy.florman@umassmed.edu



        Lab Alumni

        University of Massachusetts Medical School UMass Diego RayesDiego Rayes, Ph.D.
        Postdoctoral Fellow - 2012

        University of Massachusetts Medical School UMass Jamie Donnelly, Ph.D.
        Jamie Donnelly, Ph.D.
        Graduate Student - 2011

        University of Massachusetts Medical School UMass Jasmin Abraham
        Jasmin Abraham
        Research Technician - 2010

        University of Massachusetts Medical School UMass Sean Maguire
        Sean Maguire
        Research Technician - 2010

        University of Massachusetts Medical School UMass Adam McPherson
        Adam McPherson
        Research Technician - 2008





        Rotation Projects

        Rotation Projects

        1) Molecular and neuronal characterization of C. elegans escape behavior
        Defining sensorimotor circuits requires detailed knowledge of the neural connectivity of the nervous system, and the ability to manipulate the functions of the component neurons and to define and quantify the behavioral outputs. The simplicity and completely defined synaptic connectivity of C. elegans nervous system provides unique opportunity to dissect how neural networks control behavior.

        2) Identify genes involved in the processing, expression and subunit composition of voltage-gated calcium channels
        The release of neurotransmitter from synaptic vesicles is critical for the propagation of signals that generate behavioral outputs. Voltage-gated calcium channels provide the calcium influx essential for synaptic vesicle exocytosis. We are characterizing mutants to identify new genes involved in the proper assembly, expression and trafficking of functional calcium channels.

        3) Investigate the evolutionary origins of escape behavior
        Nematophagous fungi employ a variety of strategies to capture worms. In predator-prey experiments, we have been able to show that the suppression of head movements allows the animal to escape from constricting traps. Further investigation of the neurobiology behind the escape from predation may provide insight into how this behavior evolves.

        Contact Information:
        Mark Alkema, Ph.D.
        University of Massachusetts Medical School
        Department of Neurobiology, LRB 717
        364 Plantation Street
        Worcester, MA 01605 USA
        phone: 508-856-6158 (office)
        phone: 508-856-8541 (lab)
        e-mail: mark.alkema@umassmed.edu




        Post Docs

        A postdoctoral position is available to study in this laboratory. Contact Dr. Mark Alkema for additional details.


        Contact Information:
        Mark Alkema, Ph.D.
        University of Massachusetts Medical School
        Department of Neurobiology, LRB 717
        364 Plantation Street
        Worcester, MA 01605 USA
        phone: 508-856-6158 (office)
        phone: 508-856-8541 (lab)
        e-mail: mark.alkema@umassmed.edu




        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Shipley FB, Clark CM, Alkema MJ, Leifer AM. Simultaneous optogenetic manipulation and calcium imaging in freely moving C. elegans. Front Neural Circuits. 2014; 8:28.
          View in: PubMed
        2. Homberg U, Seyfarth J, Binkle U, Monastirioti M, Alkema MJ. Identification of distinct tyraminergic and octopaminergic neurons innervating the central complex of the desert locust, Schistocerca gregaria. J Comp Neurol. 2013 Jun 15; 521(9):2025-41.
          View in: PubMed
        3. Donnelly JL, Clark CM, Leifer AM, Pirri JK, Haburcak M, Francis MM, Samuel AD, Alkema MJ. Monoaminergic Orchestration of Motor Programs in a Complex C. elegans Behavior. PLoS Biol. 2013 Apr; 11(4):e1001529.
          View in: PubMed
        4. Schumacher JA, Hsieh YW, Chen S, Pirri JK, Alkema MJ, Li WH, Chang C, Chuang CF. Intercellular calcium signaling in a gap junction-coupled cell network establishes asymmetric neuronal fates in C. elegans. Development. 2012 Nov; 139(22):4191-201.
          View in: PubMed
        5. Pirri JK, Alkema MJ. The neuroethology of C. elegans escape. Curr Opin Neurobiol. 2012 Jan 4.
          View in: PubMed
        6. Maguire SM, Clark CM, Nunnari J, Pirri JK, Alkema MJ. The C. elegans Touch Response Facilitates Escape from Predacious Fungi. Curr Biol. 2011 Aug 9; 21(15):1326-30.
          View in: PubMed
        7. Leifer AM, Fang-Yen C, Gershow M, Alkema MJ, Samuel AD. Optogenetic manipulation of neural activity in freely moving Caenorhabditis elegans. Nat Methods. 2011 Feb; 8(2):147-52.
          View in: PubMed
        8. Koon AC, Ashley J, Barria R, Dasgupta S, Brain R, Waddell S, Alkema MJ, Budnik V. Autoregulatory and paracrine control of synaptic and behavioral plasticity by octopaminergic signaling. Nat Neurosci. 2011 Feb; 14(2):190-9.
          View in: PubMed
        9. Grove CA, De Masi F, Barrasa MI, Newburger DE, Alkema MJ, Bulyk ML, Walhout AJ. A multiparameter network reveals extensive divergence between C. elegans bHLH transcription factors. Cell. 2009 Jul 23; 138(2):314-27.
          View in: PubMed
        10. Pirri JK, McPherson AD, Donnelly JL, Francis MM, Alkema MJ. A tyramine-gated chloride channel coordinates distinct motor programs of a Caenorhabditis elegans escape response. Neuron. 2009 May 28; 62(4):526-38.
          View in: PubMed
        11. Alkema MJ. Oxygen sensation: into thick air. Curr Biol. 2009 May 26; 19(10):R407-9.
          View in: PubMed
        12. Alkema MJ, Hunter-Ensor M, Ringstad N, Horvitz HR. Tyramine Functions independently of octopamine in the Caenorhabditis elegans nervous system. Neuron. 2005 Apr 21; 46(2):247-60.
          View in: PubMed
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