Alexander M. van der Linden
Academic Unit: College of Science
Title: Assistant Professor
Research Area: Neurobiology
Graduate Programs: CMB, CMPP
M.Sc, 1999, Molecular Biology, Leiden University, NL
Ph.D, 2003, Biology, Utrecht University, NL
Postdoc, 2009, Neurobiology, Brandeis University, Waltham
Mail Stop: 314
Phone: (775) 784-6080
Fax: (775) 784-6072
Animals must alter their behavior and development in response to changing environments to survive and reproduce. This plasticity involves modifications in the response characteristics of individual neurons, which can entail neuronal activity and gene expression changes. Understanding the underlying mechanisms by which environmental signals affect an animal’s behavior and development is a fundamental question in neurobiology.
We use the nematode Caenorhabditis elegans as an attractive genetic model organism to investigate how signals from the environment control neuronal gene expression, behavior and development. What are the molecules, what are the signaling pathways and neuronal circuits that allow animals to respond to environmental signals such as food? To study these questions, we use various molecular genetic and genomic approaches in C. elegans.
Current projects in the lab are aimed at understanding two broad biological questions:
1) How do animals sense their environment, and how do they modulate their responses to a constant changing environment? As in other organisms, C. elegans is able to modulate the expression of G-protein-coupled receptor (GPCR) genes in response to environmental signals such as constitutively produced pheromone and food. This provides a simple mechanism by which C. elegans may rapidly alter its sensory behaviors and development in response to changing environmental conditions. We have identified several molecules that play key roles in the regulation of GPCR gene expression. In particular, we have found that the KIN-29/MEF-2-mediated pathway acts in the chemosensory system to regulate GPCR gene expression and food-induced responses such as body size. Our current studies are directed to better understand the KIN-29 pathway by which food-derived signals are integrated to modulate behavior and development, and to define the neuronal circuits that regulate these food-induced responses.
2) How does temperature regulate the circadian clock? Most organisms show circadian rhythms (cycles of behavior or gene expression) that repeat roughly every 24 hours. These rhythms are outputs of an internal clock synchronized by daily environmental cycles of light or temperature, and control many aspects of behavior and physiology such as sleep and metabolism. Much is known about light cycles, but it is still poorly understood how temperature is sensed and transduced by the circadian clock(s). Our current research is aimed at understanding the mechanisms of cycling gene expression and the molecular clock in response to temperature cycles and to describe the behavioral consequences.
Current Graduate Students
Tianyuan Cui (CMPP Ph.D. program)
Katie Eyer (Research Associate)
Van der Linden, A.M., Beverley, M., Kadener, S., Rodriguez, J., Wasserman, S., Rosbash, M. and Sengupta, P. (2010) Genome-wide analysis of light and temperature-entrained circadian transcripts in C. elegans. PloS Biol. Oct 12;8(10):e1000503
Nokes, E., Van der Linden, A.M., Mukhopadhyay, S., and Sengupta, P. (2009) Cis-regulatory mechanisms of gene expression in an olfactory neuron type in C. elegans. Developmental Dynamics, Dec; 238(12): 3080-92.
Van der Linden, A.M., Wiener S., You Y., Kim K., Avery L., and Sengupta, P. (2008) The EGL-4 PKG acts with the KIN-29 SIK and PKA to regulate chemoreceptor gene expression and sensory behaviors in C. elegans. Genetics Nov; 180(3): 1475-91.
Van der Linden, A.M., Nolan, K.M., and Sengupta, P. (2007) KIN-29 SIK regulates chemoreceptor gene expression via an MEF2 transcription factor and a class II HDAC. EMBO J. 26(2): 358-70.
Bauer Huang S.L., Saheki Y., VanHoven M.K., Torayama I., Ishihara T., Katsura I., Van der Linden A., Sengupta P. and Bargmann C.I. (2007) Left-right olfactory asymmetry results from antagonistic functions of voltage-activated calcium channels and the Raw repeat protein OLRN-1 in C. elegans. Neural Develop. Nov 6: 2:24.
Fitzgerald K., Tertyshnikova S., Moore L., Bjerke L., Burley B., Cao J., Carroll P., Choy R., Doberstein S., Dubaquie Y., Franke Y., Kopczynski J., Korswagen H., Krystek S.R., Lodge N.J., Plasterk R., Starrett J., Stouch T., Thalody G., Wayne H., Van der Linden A., Zhang Y., Walker S.G., Cockett M., Wardwell-Swanson J., Ross-Macdonald P. and Kindt R.M. (2006) Chemical genetics reveals an RGS/G-protein role in the action of a compound. PLoS Genet. 2(4)
Van der Linden, A.M. and Plasterk, R.H.A. (2004) Shotgun cloning of transposon insertions in the genome of Caenorhabditis elegans. Comp Funct Genomics 5(3): 225-29.
Simmer, F.*, Moorman, C.*, Van der Linden, A.M.*, Kuijk, E., van den Berghe, P.V., Kamath, R., Fraser, A.G., Ahringer, J., and Plasterk, R.H.A. (2003). Genome-wide RNAi of C. elegans using the hypersensitive rrf-3 strain reveals novel gene functions. PLoS Biol. 1: 77-84.
* authors contributed equally
Van der Linden, A.M., Moorman, C., Cuppen, E., Korswagen, H.C. and Plasterk, R.H.A. (2003) Hyperactivation of the G12-mediated signaling pathway in Caenorhabditis elegans induces a developmental growth arrest via protein kinase C. Current Biology 13: 516-521.
Cuppen E., Van der Linden A.M., Jansen G. and Plasterk R.H. (2003) Proteins interacting with Caenorhabditis elegans Gα subunits. Comp Funct Genomics 4(5): 479-91.
Van der Linden, A.M., Simmer, F., Cuppen, E., and Plasterk, R.H.A. (2001) The G-protein β subunit GPB-2 in Caenorhabditis elegans Regulates the Goα-Gqα Signaling network through interactions with the regulator of G-protein signaling proteins EGL-10 and EAT-16. Genetics 158: 221-235.
Korswagen, H.C., Van der Linden, A.M. and Plasterk, R.H.A. (1998) G-protein hyperactivation of the Caenorhabditis elegans adenylyl cyclase SGS-1 induces neuronal degeneration. EMBO J. 17: 5059-5065
Faculty by research area
- Mastick, C
- Mastick C.
- Mastick G.
- Van der Linden
- von Bartheld
- von Bartheld