straight lab Members
Aaron Straight Ph.D.
Associate Professor of Biochemistry
Ph.D. in Biochemistry (U.C. San Francisco)
Our work is directed at understanding the mechanisms that ensure high fidelity genome maintenance and segregation in eukaryotes. We use a wide variety of experimental systems ranging from yeasts and flies to frogs and humans in order to address biophysical, biochemical and cell biological questions in chromosome biology. We are particularly interested in how cells accurately segregate chromosomes to daughter cells during mitosis and meiosis to produce viable daughters and gametes so that an organism can grow, develop and proliferate. Our research has focused on understanding how the chromosomal centromere and kinetochore function to link the chromosomes to the mitotic spindle that segregates chromosomes during division. We are also interested in how chromosomes are organized within the interphase nucleus and mitotic chromosome so that the genome can be actively transcribed, replicated and segregated and yet accurately maintained and packaged within the nucleus and cell.
Current Lab Members
Graduate Student in Biochemistry
I'm interested in how the epigenetic identity of centromeric chromatin is maintained through successive cell divisions. I use a combination of biochemical and cell biological tools -- including cell-free reconstitution of centromere assembly in Xenopus egg extract -- to study how the assembly of CENtromere Protein A (CENP-A) is carried out with spatial and temporal specificity.
The centromere is a specialized DNA locus that is absolutely essential for correct chromosome segregation during cell division. I am developing novel biochemical techniques to study how the underlying chromatin of the centromere, defined by nucleosomes containing CENP-A, is maintained through the cell cycle. I am building centromeres in vitro using recombinant histones, purified DNA and Xenopus Laevis egg extracts. My work centers on 1) how CENP-A nucleosomes epigenetically promote the assembly of new CENP-A nucleosomes 2) how CENP-A nucleosomes are segregated during DNA replication, and 3) how other centromere proteins regulate these processes.
Molecular genetics isn't just the study what genes you have, but also how those genes are spatially and temporally organized to encode the functional architecture of the genome. Two components of nuclear architecture are of particular interest to me. First, I am interested in the spatiotemporal organization of the centromere, and am developing methods to visualize its assembly, maturation and turnover on single chromatin fibers. Orthogonally, I am also interested in the global architecture of nuclear chromatin defined by the insulator and boundary protein CTCF, which has pleiotropic functions that are essential for proper embryonic development, cell differentiation and tumor suppression. Pursuant to both of these interests, I am using advanced imaging methods to visualize the structural dynamics of both reconstituted chromatin fibers and chromatin in living cells.
I'm studying two aspects of centromere dynamics: 1) The influence of centromeric chromatin organization on centromere function and 2) how proteins of the centromere and kinetochore complexes interact in a cell cycle-specific manner to assemble a functional kinetochore during mitosis and meiosis. I use a combination of two main techniques, the cell-free assembly of centromeres and kinetochores in Xenopus egg extract (developed in this lab) and single molecule imaging of chromatin arrays.
The centromere is a unique region on the chromosome that specifies the site of microtubule attachment and thus regulates chromosome segregation. This region is specified epigenetically by the presence of CenpA, a histone H3 variant. So far, two centromere proteins have been shown to directly interact with CenpA: CenpC and CenpN. I am interested in how CenpN regulates CenpA incorporation into centromeric chromatin and centromere formation.
Julio Cesar Flores-Servin
Chromatin based epigenetic information can be stably inherited through generations yet we have a poor understanding of how that information is encoded, replicated and maintained in cells. I am using the centromere as a model for studying epigenetic inheritance to understand how chromatin distributed during DNA replication is regenerated in each cell cycle.
Rene Ladurner Ph.D.
Each cycle of DNA replication duplicates the genome but also distributes chromatin proteins between newly duplicated daugter DNA strands. In order to maintain epigenetic information in chromatin the cell must regenerate chromatin states in each cell cycle. I am studying the coupling between DNA replication and chromatin maintenance to understand the mechanisms of epigenetic inheritance.
Joint with other labs
Graduate Student in Chemical Engineering (Spakowitz Lab)
I'm interested in the biophysics of chromosome organization and motion. I develop physical models for the motion of chromosomal DNA that are inspired by theory from polymer physics and can be directly compared to experimental measurements using fluorescent locus tracking in live cells.
Viviana Risca Ph.D.
Post-doctoral Fellow in Genetics (Greenleaf Lab, Genetics)
I am interested in the mechanisms that organize chromatin at intermediate length scales and the role that chromatin compaction plays in regulating chromatin accessibility, gene expression, and the biophysical properties of chromosomes. I use a high-throughput sequencing approach to develop new methods for studying the in vivo three-dimensional structure of chromatin on the 100 bp to kb length scale.
The early embryo is dependent on the maternal stores of biological macromolecules for its first divisions. As the embryo grows, the control of division and development is transferred to the zygote. I am interested in how the zygotic genome is activated during the development of the early embryo and the signals that initiate the process of zygotic genome activation.
I am interested in how eukaryotic genomes are organized in the nucleus and how the organization of the genome impacts its functional properties. I am using single molecule spectroscopic methods to understand how the CTCF protein organizes long range interactions between different genomic loci.
Former Lab Members
Teddy Yewdell, Ph.D., Post-doctoral Fellow, MSKCC, (Jayanta Chadhuri Lab)
Annika Guse, Ph.D., Assistant Professor, University of Heidelberg (Center for Organismal Studies)
Colin Fuller, Ph.D., Data Scientist/Engineer, Khan Academy
Ben Moree, Ph.D., Senior Scientist, Biodesy
Topher Carroll, Ph.D., Assistant Professor, Yale University (Department of Cell Biology)
Rebecca Purdom, J.D. Vermont Law School
Laila Strickland, Ph.D., Scientist, 108Labs
Kristina Godek, Ph.D., Post-doctoral Fellow, Dartmouth College (Duane Compton Lab)
Kristin Milks, Ph.D., Teacher, Bloomington High School South
Ian Brennan, Ph.D., Scientist, Amunix
Craig Betts, Ph.D., Scientist, Clontech
Dina Finan, Ph.D., Scientist, Genencor
Corey Meyer, Ph.D., Senior Analyst, Gryphon Scientific
Amanda Amodeo, Lewis Sigler Fellow, Princeton University
Justin Smith, Undergraduate Summer Student, Catawba College
Marieke Rozendaal, Research Assistant, IRIC
Caroline Horn, Scientist, Pioneer Hi-Bred International
Melanie Santos-Marrero, Graduate Student in Immunology, U. Penn
Mark Kelly, Graduate Student in Structural Biology, Stanford University
Andy Nguyen, Medical Student, Harvard Medical, School
Anthony Cordova, Intern, Genentech
Whitney Johnson, Graduate Student