Special LSF Seminar with Christoph & Thomas Cremer

40 years of joint research to explore the functional nuclear architecture

Christoph Cremer

Ordinarius, Head Lightoptical Nanoscopy at IMB Heidelberg, DE

Kirchhoff Institute of Physics (KIP)/Institute for Pharmacy & Molecular Biotechnology (IPMB)

"From Laser-UV-Microbeam Irradiation to Super-Resolution Fluorescence Microscopy"

Thomas Cremer

Professor for Anthropology and Human Genetics, LMU Biozentrum, Martinsried /DE

"From Experimental Proof of Chromosome Territories to the Chromosome Territory - Interchromatin Compartment (CT-IC) Model"

Venues:

• Leica Scientific Forum Los Angeles:
  November 1, 2011, 3:00-04:30pm - Chairman: Shimon Weiss
  Venue: Auditorium of the California NanoSystems Institute (CNSI), UCLA, Building 114, 570 Westwood Plaza, Los Angeles, CA 9009
• Leica Scientific Forum San Diego
  November 2, 2011, 3:00-04:30pm - Chairman: Mark Ellisman
  Venue: Auditorium of Skaggs School of Pharmacy & Pharmaceutical Sciences, UCSD, 9500 Gilman Drive, MC 0657, La Jolla

• Leica Scientific Forum San Francisco
  November 3, 2011, 3:30-5:00pm - Chairman: Michael Stryker
  Venue: UCSF Mission Bay, Genentech Hall Auditorium, 600 16th St., San Francisco

The Scientific Advisory Board US-West -

Prof. Dr. Mark Ellisman, University of California San Diego (UCSD),

Prof. Dr. Roger Tsien, University of California San Diego (UCSD),

Prof. Dr. Shimon Weiss, University of California Los Angeles (UCLA),

Prof. Dr. Katsushi Arisaka, University of California Los Angeles (UCLA),

Prof. Dr. Arnold Kriegstein, University of California San Francisco (UCSF),

Prof. Dr. Michael Stryker, University of California San Francisco (UCSF)

and Dr. Thomas Zapf (Leica Microsystems) -

invites you to join the post lecture receptions in each of the locations.

Registration:

All lectures are free of charge. For organizational reasons please RSVP to the following adress: lsf@leica-microsystems.com.

Abstracts

The hypothesis of chromosome territories (CTs) was first proposed by Carl Rabl (1885) and Theodor Boveri (1909), but later abandoned. During the 1970ies and 80ies this hypothesis was experimentally proven both by laser-uvmicrobeam studies and in situ hybridization experiments. Since then we have developed methods for quantitative studies of CT organization and arrangements in the cell nucleus. The results of these studies led to the CT-IC model of nuclear architecture. The interchromatin-compartment (IC) forms an interconnected 3D system of IC-channels (width <400 nm) and IC-lacunas (width >400 nm). It starts/ends with small channels at the nuclear pores and expands both between CTs and throughout the interior of CTs. Splicing speckles and nuclear bodies are located within the IC and recent evidence suggests that the IC also serves as a preferred route for the transport of RNPs. CTs are built up from a network of interconnected ~1 Mb chromatin domains (~1Mb CDs), i.e. domains with a DNA-content in the order of 1 Mb. Clusters of ~1Mb CDs can form still larger CDs. Replicating ~1Mb CDs can be visualized during S-phase as replication foci, but they persist as basic units of higher order chromatin organization at any stage of interphase.

To which extent ~1Mb CDs persist as indivdidual entitities during the transformation of CTs into mitotic chromosomes and into nuclei of the next cell generation remains to be established. The structure of ~1Mb CDs has not yet been resolved, but we argue that each ~1Mb CD is built up from a series of ~100 kb chromatin domains (~100 kb CDs), i.e. more or less compacted chromatin loop domains with a DNA content in the order of 100 kb. Direct contacts between neighboring ~1Mb CDs provide ample opportunities for interactions in cis (within a given CT) or trans (between neighboring CTs), including the formation of intra- and interchromosomal rearrangements. The perichromatin region (PR) represents an about 100 nm thick layer of decondensed chromatin, located at the periphery of CDs. It constitutes the nuclear compartment for transcription, splicing, DNA-replication and possibly also DNA-repair and separates the highly compact, transcriptionally silent interior of CDs from the IC. Accordingly the 3D organization of a CT can be compared with a sponge built up from a 3D network of chromatin domains permeated by the IC.

It should be noted that constrained Brownian movements of CDs in the nucleus of living cells result in continuous changes of the width of IC channels providing dynamic opportunities for normal or pathological interactions. The interior of IC lacunas is free of chromatin and harbors nuclear bodies and splicing speckles. This structural organization allows direct functional interactions between the IC and the PR, such as the delivery of splicing components from splicing speckles to sites of co-transcriptional splicing.

Learn more: http://www.leica-microsystems.com/events/leica-scientific-forum/