Group Christopher Campbell

Causes and Consequences of Chromosomal Instability

On this page

The Question

During cell division, errors made during the distribution of chromosomes to the daughter cells result in cells with an abnormal number of chromosomes, which is called aneuploidy. Aneuploidy is the cause of the majority of miscarriages and is also present in ~90 percent of solid tumors. Paradoxically, aneuploidy is universally harmful to cellular fitness, but can be advantageous to the cells under selective conditions. In the Campbell lab, we study how specific patterns of aneuploid chromosomes are selected for over time and how aneuploidy affects cellular physiology and drug resistance.

The Approach

Aneuploidy has historically been very challenging to study as it affects the expression levels of hundreds of functionally unrelated genes simultaneously. To address this challenge, we have developed innovative bottom-up approaches to study aneuploidy including: 1) in vitro evolution methods for observing how aneuploidy patterns develop over time, 2) techniques for engineering aneuploidy in both yeast and human cells, and 3) ways of creating partial chromosome amplifications/deletions to determine which parts of chromosomes are primarily responsible for aneuploidy phenotypes. We have developed these methods in both yeast and human cells to facilitate both high throughput and more disease-related research.

Christopher Campbell

Chris Campbell received his PhD in biochemistry and cell biology from the University of California San Francisco. He then conducted a postdoctoral fellowship at the University of California San Diego before forming his own group at the Max Perutz Labs in 2015.

Download CV

Main Building
Room: 5.614

   +43 1 4277 74418

Spotlights

The development of aneuploidy patterns over time in yeast and human cells.

Different cancer types have distinct patterns of aneuploidy that they acquire over time, with some specific aneuploid chromosomes being present in the vast majority of certain cancers. Often, these patterns are very complex, consisting of many different chromosome gains and losses in the same tumor.  We have therefore developed methods to observe the formation of complex aneuploid karyotypes over time to investigate what factors determine the selection of such patterns. These studies have revealed many basic principles underlying aneuploidy selection.

Combinatorial effects of many genes on aneuploidy phenotypes.

Aneuploidy is generally bad for the growth and viability of cells due to imbalances in gene expression between chromosomes. It is therefore surprising how frequently aneuploid chromosomes arise as adaptive mechanisms instead of other, more targeted mutations. One reason for this may be that aneuploidy has the ability to alter the expression of many different genes at the same time. We have therefore developed methods for systematically analyzing how combinatorial effects of genes lead to strong aneuploidy phenotypes.

Chromosome segregation and aneuploidy in meiosis.

Aneuploidy resulting from defects in chromosome segregation during meiosis is the cause of the majority of miscarriages. We are working to uncover novel mechanisms regulating meiotic chromosome segregation to determine what makes this process uniquely error-prone. In addition, we are testing the possibility that meiosis provides a barrier to adaptation via aneuploidy.

    Team

    Christopher Campbell
    Group Leader
       +43 1 4277 74418
    Room: 5.614

    Ananya Dodamani
    PhD Student
       +43 1 4277 52808
    Room: 5.512

    Rodina Genidy
    PhD Student
       +43 1 4277 00000
    Room: 5.512

    Clara Hackethal
    Master Student
       +43 1 4277 52808
    Room: 5.512

    Manuela Sophie Koller
    PhD Student
       +43 1 4277 52808
    Room: 5.512

    Katharina Nittnaus
    Lab Technician
       +43 1 4277 52808
    Room: 5.512

    Lisa Pulferer
    Master Student
       +43 4277 00000
    Room: 5.512

    Virag Tarcsa
    Master Student
       +43 1 4277 52808
    Room: 5.512

    Rustam Tuktarov
    Bachelor Student
       +43 4277 00000
    Room: 5.512

    Selected Publications

    Adaptation to high rates of chromosomal instability and aneuploidy through multiple pathways in budding yeast.

    2023 The EMBO journal;42(8):e111500.
    PMID:  36530167

    Clarke Matthew N, Marsoner Theodor, Adell Manuel Alonso Y, Ravichandran Madhwesh C, Campbell Christopher S

    Aurora B activity is promoted by cooperation between discrete localization sites in budding yeast.

    2022 Molecular biology of the cell;33(9):ar85.
    PMID:  35704464

    Marsoner Theodor, Yedavalli Poornima, Masnovo Chiara, Fink Sarah, Schmitzer Katrin, Campbell Christopher S

    Adaptation to spindle assembly checkpoint inhibition through the selection of specific aneuploidies.

    2023 Genes & development;37(5-6):171, 190, 171-190.
    PMID:  36859339

    Adell Manuel Alonso Y, Klockner Tamara C, Höfler Rudolf, Wallner Lea, Schmid Julia, Markovic Ana, Martyniak Anastasiia, Campbell Christopher S

    Collaborations & Funding

    Special Research Programme "Meiosis"

    Christopher Campbell is part of the SFB "Meiosis"

     

     

    WWTF - Vienna Science and Technology Fund

    The Campbell Group is supported through the "Vienna Research Groups for Young Investigators" program.

    Doctoral Program "Chromosome Dynamics"

    The Campbell group participates in in the special Doctoral Program 'Chromosome Dynamics' reviewed and funded by the Austrian Research Fund FWF.

    FWF

    START Grant 

    21