Heads of Laboratories
Vice President for Academic Affairs
Richard and Jeanne Fisher Professor
Laboratory of Genetics
Dr. Young studies the biological clocks that govern the timing of an organism’s daily activities. He is interested in how circadian rhythms arise from interactions among certain genes and their proteins, which set up molecular oscillations. His lab’s findings have implications for sleep and mood disorders, as well as dysfunctions related to the timing of gene activity underlying vision, locomotion, metabolism, immunity, learning, and memory.
Biological clocks are internal mechanisms that control the timing of daily activities in living organisms. In Drosophila melanogaster, these circadian clocks are regulated by a small group of genes including per (period), tim (timeless), dbt (double-time), clk (clock), cyc (cycle), sgg (shaggy), Pdp1 (PAR domain protein 1), and vri (vrille) loci. Mutations in any of these genes can lengthen or shorten the period of behavioral and other circadian rhythms, or abolish the rhythms altogether. The abundance of per, tim, vri, Pdp1, and clk RNA and their encoded proteins changes rhythmically with a circadian period. Mutations affecting any of these genes have corresponding effects on behavioral and molecular rhythms.
Dr. Young has been studying circadian clocks for nearly three decades with a focus on their cellular and molecular machinery. Research from the Young lab led to the discovery of most of the genes listed above. Two of them make key proteins, TIM and PER, that shift their subcellular location in a 24-hour cycle. Dr. Young and his colleagues found these proteins accumulate, pair up in the cell’s cytoplasm, and migrate into the nucleus, where their presence stops their production by shutting down the per and tim genes. These events are strictly timed within the cell, as PER and TIM are retained in the cytoplasm for a fixed interval of several hours. This delay promotes RNA and protein rhythms, and determines the period of the clock. Another of the lab’s discoveries is that the enzyme casein kinase 1 (DBT) regulates the pace of this 24-hour molecular clock by restricting the longevity of the PER protein. Others have recently shown that faulty interactions between casein kinase 1 and PER cause certain heritable sleep disorders in humans.
Dr. Young’s laboratory has used oligonucleotide microarrays that represent all 14,000 fly genes to study the gene expression programs regulated by the molecular clock. They have found that in the Drosophila head, approximately 400 to 500 genes — about six to seven percent of all genes active in the head — are expressed with a circadian rhythm. Genes composing this large circadian program influence almost every aspect of the fly’s biology, and subsets of these genes switch on and off with phases representing every hour of the day and night. When genes of the clock are mutated, this program of temporally sequenced gene expression disappears even if environmental cycles are present, indicating the temporal program is thoroughly dependent on the molecular oscillator.
Recently, members of the Young laboratory have identified genes that affect the homeostatic regulation of sleep in Drosophila, uncovering specific neurons whose activity promotes sleep. They have also begun to study sleep and circadian rhythms at the genetic and molecular levels in humans. The latter work involves collaborative studies of circadian behavioral and physiological rhythms that are coupled to studies in the Young laboratory that assess rhythmic gene and protein activities established in cultured cells derived from patients with certain sleep and depressive disorders.
B.A. in biology, 1971
Ph.D. in genetics, 1975
University of Texas, Austin
Stanford University School of Medicine, 1975–1977
Assistant Professor, 1978–1984
Associate Professor, 1984–1988
Vice President for Academic Affairs, 2004–
The Rockefeller University
Howard Hughes Medical Institute
National Institutes of Health MERIT Award, 2007
Peter and Patricia Gruber Foundation Neuroscience Prize, 2009
Louisa Gross Horwitz Prize, 2011
Canada Gairdner International Award, 2012
Massry Prize, 2012
Shaw Prize, 2013
Wiley Prize, 2013
National Academy of Sciences
Jang, A.R. et al. Drosophila TIM binds importin α1, and acts as an adapter to transport PER to the nucleus. PLoS Genet. 11, e1004974 (2015).
Vaidya, A.T et.al. Flavin reduction activates Drosophila cryptochrome. Proc. Natl. Acad. Sci. U.S.A. 110, 20455–20460 (2013).
Rogulja, D. and Young, M.W. Control of sleep by cyclin A and its regulator. Science 335, 1617–1621 (2012).
Stavropoulos, N. and Young, M.W. insomniac and Cullin-3 regulate sleep and wakefulness in Drosophila. Neuron 72, 964–976 (2011).
Zoltowski, B.D. et al. Structure of full-length Drosophila cryptochrome. Nature 480, 396–399 (2011).