Douglas Chalker

Professor of Biology​
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    • Washington University
    • CB 1137
    • One Brookings Drive
    • St. Louis, MO 63130-4899
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    Professor Chalker's laboratory studies a remarkable process of chromosomal rearrangement that occurs during development of the ciliated protozoan Tetrahymena thermophila. His research aims to ultimately learn fundamental principles governing chromosome structure and genetic stability.

    RNA interference (RNAi)-related mechanisms participate in diverse epigenetic phenomena. Few are more extreme than the genome remodeling of the ciliate Tetrahymena thermophila. This organism eliminates nearly 15 megabases of its germline DNA from the somatic nucleus during its development.

    The Chalker lab aims to understand the regulation of this massive genome reorganization using a combination of genetic, molecular, and cellular biology approaches to uncover how ~6000 DNA segments are selectively excised. The current model is built on the observations that bi-directional germline transcription leads to the generation of 28-30 base RNA molecules (scan RNAs) that then target specific chromatin modification(s) to the homologous locus. The DNA rearrangement machinery recognizes the modified chromatin state and eliminates the targeted DNA segment.

    These studies will certainly provide fundamental insight into RNAi-related mechanisms that direct chromatin modifications that are critical for transcriptional gene silencing and heterochromatin formation in eukaryotes. Underlying this proposal is a goal to understand how RNA molecules can communicate genetic information between the parental and developing genomes, which has great potential to reveal novel roles for RNA in epigenetic programming. Additionally, we believe many of the DNA segments targeted for elimination are important for germline chromosome structure and thus understanding how the cell specifically recognizes these sequences will contribute general knowledge of mechanisms ensuring chromosome stability that are essential to prevent aberrant rearrangements.

    recent courses

    Eukaryotic Genomes

    An advanced exploration of the structure and function of DNA within the eukaryotic nucleus. Lecture and discussion cover topics of chromatin and chromosome structure, control of gene transcription, RNA processing, and DNA replication and repair. The relevance of these topics to the genetic basis of human disease is discussed. Throughout, the experimental data that shape our current understanding are emphasized. Course grades based on exams, problem sets and short papers. Lecture 3 hours per week plus required discussion section meeting every other week. Prerequisites: Bio 2970, Chem 261 (may be taken concurrently). Offered every other fall in even numbered years.

      Laboratory Experiments with Eukaryotic Microbes

      This research-intensive course provides an introduction to diverse molecular and cytological techniques used in model experimental organisms to explore fundamental biological questions. Experiments are performed using selected fungi and protozoans commonly used in major research efforts. Emphasis is placed on choosing the appropriate organism for the question posed using the most current technologies. Each student selects an uncharacterized gene to study in detail, conducting an original research project. Writing assignments model the components of scientific articles with the final paper reporting the cumulative findings of the semester-long project. Students also present their research during the poster session of the undergraduate research symposium. Prerequisites: Bio 2960 and 2970 and permission of instructor-- contact instructor early to ensure enrollment. One hour of lecture and six hours of laboratory a week. Fulfills the upper-level laboratory requirement for the Biology major and is writing intensive. Enrollment limited to 16.

        Molecular Biology on the Cutting Edge

        Recent biomedical discoveries have been greatly advanced through the development of innovative, state-of-the-art techniques. For example, Nuclear Magnetic Resonance (NMR) has proved to be an invaluable tool in both efforts to determine the atomic structure of proteins and small molecules as well as in clinical settings. This course introduces students to a variety of cutting-edge laboratory techniques and discusses the impact of these techniques on biology and medicine. Students have the unique opportunity to learn from graduate students employing these approaches in their doctoral studies. Topics include: human brain neuroimaging, next-generation DNA sequencing, CRISPR-Cas gene editing and many more. Weekly classes consist of a 30-45 minute presentation on a particular technique, followed by 60-minute discussion of the assigned readings. Students will be evaluated on class participation, answers to weekly research based questions and two longer written assignments. Prerequisites: Biology 2960 and 2970 and at least one semester of BIO500 or equivalent research experience approved by the course master.

          Selected Publications

          Malone C.D., A. M. Anderson, J. A. Motl, C. H. Rexer, and  D. L. Chalker. (2005) Germline transcripts are processed by a Dicer-like protein that is essential for developmentally programmed genome rearrangements of Tetrahymena thermophila. Mol. Cell. Biology 25(20):9151-64.

          Charles H. Rexer and D L. Chalker. (2007) Lia1p, a Novel Protein Required during Nuclear Differentiation for Genome-Wide DNA Rearrangements in Tetrahymena thermophila.  Eukaryotic Cell 6(8):1320-1329

          Malone CD, Falkowska KA, Li AY, Galanti SE, Kanuru RC, LaMont EG, Mazzarella KC, Micev AJ, Osman MM, Piotrowski NK, Suszko JW, Timm AC, Xu MM, Liu L, Chalker DL. (2008) Nucleus-specific importin alpha proteins and nucleoporins regulate protein import and nuclear division in the binucleate Tetrahymena thermophila. Eukaryot Cell. 7:1487-99

          Chalker DL, Meyer E, Mochizuki K. (2013) Epigenetics of ciliates. Cold Spring Harb Perspect Biol. 2013 Dec 1;5(12):a017764. doi: 10.1101/cshperspect.a017764. PMID: 24296171

          Shieh AW, and DL Chalker (2013) LIA5 Is Required for Nuclear Reorganization and Programmed DNA Rearrangements Occurring during Tetrahymena Macronuclear Differentiation. PLoS One. 2013 Sep 17;8(9):e75337. PMID: 24069402

          Schwope RM and DL Chalker (2014) Mutations in Pdd1 reveal distinct requirements for its chromo- and chromoshadow domains in directing histone methylation and heterochromatin elimination. Eukaryotic Cell 2014, 13(2):190-201. PMID: 24297443

          Horrell SA, Chalker DL. (2014) LIA4 encodes a chromoshadow domain protein required for genomewide DNA rearrangements in Tetrahymena thermophila. Eukaryot Cell. 2014 Oct;13(10):1300-11.