Catarina A. Marques- PhD
- PostDoc Research Associate at University of Glasgow
Catarina A. Marques
- PhD
- PostDoc Research Associate at University of Glasgow
About
36
Publications
120,849
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
418
Citations
Introduction
I'm back working on DNA replication in Leishmania at the University of Glasgow, following up findings resultant from my PhD, during which I studied the initiation of DNA replication in both Trypanosoma brucei and Leishmania (check out my 3MT competition presentation at http://www.youtube.com/watch?v=9IVm6vJGQNA?). In the interim, I was at the University of Dundee, where I worked on T. brucei VSG mono allelic expression and cell cycle. Before moving to Scotland, was an BSc and MSc student at the University of Lisbon, where I worked in malaria at the IMM. Last year I performed at Bright Club in Dundee, communicating science via stand-up comedy; check it out https://www.youtube.com/watch?v=bUIXWgWA_Tg&list=PL6kJ7BgSa5IvE1YQmOmhMObZijfAg9r8A&t=0s&index=4
Current institution
Additional affiliations
December 2018 - present
January 2016 - November 2018
July 2015 - December 2015
Position
- Post Doctoral Research Assistant
Description
- 6-month project, following up a project started during my PhD: initiation of DNA replication in T. brucei and Leishmania
Education
April 2011 - July 2015
September 2009 - December 2010
September 2005 - July 2009
Publications
Publications (36)
Bloodstream-form African trypanosomes display mono-telomeric expression of a Variant Surface Glycoprotein (VSG) gene in an inter-chromosomally bridged transcription and splicing compartment, such that the dominant gene produces 10,000 times more transcript than excluded VSG genes. Antigenic variation, whereby parasites switch to express other VSGs,...
Genomes in eukaryotes normally undergo DNA replication in a choreographed temporal order, resulting in early and late replicating chromosome compartments. Leishmania, a human protozoan parasite, displays an unconventional DNA replication program in which the timing of DNA replication completion is chromosome size-dependent: larger chromosomes compl...
The Trypanosoma brucei genome is structurally complex. Eleven megabase-sized chromosomes each comprise a transcribed core flanked by silent subtelomeres, housing thousands of Variant Surface Glycoprotein (VSG) genes. Additionally, hundreds of sub-megabase chromosomes contain 177 bp repeats of unknown function, and VSG transcription sites localise t...
Understanding genome duplication requires characterisation of the locations where DNA replication initiates, termed origins. Genome-wide mapping of DNA replication origins has mainly been derived from population-based techniques, with only a few studies examining origin location and usage at the single-cell or single-molecule level. Leishmania are...
The genome of Trypanosoma brucei is structurally complex. Eleven megabase-sized chromosomes each comprise a transcribed core flanked by silent subtelomeres, housing thousands of Variant Surface Glycoprotein (VSG) genes. Additionally, silent VSGs are also found on hundreds of sub-megabase chromosomes that harbour 177 bp repeats of unknown function,...
Genomes in eukaryotes normally undergo DNA replication in a choreographed temporal order, resulting in early and late replicating chromosome compartments. Leishmania , a human protozoan parasite, displays an unconventional DNA replication program in which the timing of DNA replication completion is chromosome size-dependent: larger chromosomes comp...
UPF1-like helicases play roles in telomeric heterochromatin formation and X-chromosome inactivation, and also in monogenic variant surface glycoprotein (VSG) expression via VSG exclusion-factor-2 (VEX2), a UPF1-related protein in the African trypanosome. We show that VEX2 associates with chromatin specifically at the single active VSG expression si...
RNA–DNA hybrids are epigenetic features of all genomes that intersect with many processes, including transcription, telomere homeostasis, and centromere function. Increasing evidence suggests that RNA–DNA hybrids can provide two conflicting roles in the maintenance and transmission of genomes: They can be the triggers of DNA damage, leading to geno...
RNA-DNA hybrids are epigenetic features of genomes that provide a diverse and growing range of activities. Understanding of these functions has been informed by characterising the proteins that interact with the hybrids, but all such analyses have so far focused on mammals, meaning it is unclear if a similar spectrum of RNA-DNA hybrid interactors i...
RNA-DNA hybrids are widespread epigenetic features of genomes that provide a growing range of activities in transcription, chromatin and DNA replication and repair. Understanding of these diverse functions has been advanced by characterising the proteins that interact with the hybrids, with all such studies revealing hundreds of potential interacto...
African trypanosomes proliferate as bloodstream forms and procyclic forms in the mammal and tsetse fly midgut, respectively. This allows them to colonise the host environment upon infection and ensure life cycle progression. Yet, understanding of the mechanisms that regulate and drive the cell replication cycle of these forms is limited. Using sing...
RNA-DNA hybrids are epigenetic features of all genomes that intersect with many processes, including transcription, telomere homeostasis and centromere function. Increasing evidence suggests RNA-DNA hybrids can provide two conflicting roles in the maintenance and transmission of genomes: they can be the triggers of DNA damage, leading to genome cha...
Trypanosomatids, which include major pathogens of humans and livestock, are flagellated protozoa for which cell cycle controls and the underlying mechanisms are not completely understood. Here, we describe a genome-wide RNA-interference library screen for cell cycle defects in Trypanosoma brucei. We induced massive parallel knockdown, sorted the pe...
The genomes of all organisms are read throughout their growth and development, generating new copies during cell division and encoding the cellular activities dictated by the genome's content. However, genomes are not invariant information stores but are purposefully altered in minor and major ways, adapting cellular behaviour and driving evolution...
DNA replication is needed to duplicate a cell's genome in S-phase and segregate it during cell division. Previous work in Leishmania detected DNA replication initiation at just a single region in each chromosome, an organisation predicted to be insufficient for complete genome duplication within S-phase. Here, we show that acetylated histone H3 (Ac...
DNA replication is needed to duplicate a cell’s genome in S phase and segregate it during cell division. Previous work in Leishmania detected DNA replication initiation at just a single region in each chromosome, an organisation predicted to be insufficient for complete genome duplication within S phase. Here, we show that acetylated histone H3 (Ac...
DNA replication is needed to duplicate a cell’s genome in S phase and segregate it during cell division. Previous work in Leishmania detected DNA replication initiation at just a single region in each chromosome, an organisation predicted to be insufficient for complete genome duplication within S phase. Here, we show that acetylated histone H3 (Ac...
Trypanosomatids, which include major pathogens of humans and livestock, are divergent eukaryotes for which cell cycle controls and the underlying mechanisms are not completely understood. Here, we describe a genome-wide RNA-interference library screen for cell cycle regulators in bloodstream form Trypanosoma brucei . We induced massive parallel kno...
Background:
DNA replication in trypanosomatids operates in a uniquely challenging environment, since most of their genomes are constitutively transcribed. Trypanosoma cruzi, the etiological agent of Chagas disease, presents high variability in both chromosomes size and copy number among strains, though the underlying mechanisms are unknown.
Resul...
Understanding the rate and patterns of genome variation is becoming ever more amenable to whole-genome analysis through advances in DNA sequencing, which may, at least in some circumstances, have supplanted more localized analyses by cellular and genetic approaches. Whole-genome analyses can utilize both short- and long-read sequence technologies....
Once every cell cycle, DNA replication takes place to allow cells to duplicate their genome and segregate the two resulting copies into offspring cells. In eukaryotes, the number of DNA replication initiation loci, termed origins, is proportional to chromosome size. However, previous studies have suggested that in Leishmania, a group of single-cell...
Chromosome damage must be repaired to prevent the proliferation of defective cells. Alternatively, cells with damage must be eliminated. This is true of human and several other cell types but may not be the case for single-celled parasites, such as trypanosomes. African trypanosomes, which cause lethal diseases in both humans and livestock, can act...
In trypanosomatids, etiological agents of devastating diseases, replication is robust and finely controlled to maintain genome stability and function in stressful environments. However, these parasites encode several replication protein components and complexes that show potentially variant composition compared with model eukaryotes. This review fo...
Introduction:
Understanding how the nuclear genome of kinetoplastid parasites is replicated received experimental stimulus from sequencing of the Leishmania major, Trypanosoma brucei and Trypanosoma cruzi genomes around 10 years ago. Gene annotations suggested key players in DNA replication initiation could not be found in these organisms, despite...
All pathogens must survive host immune attack and, amongst the survival strategies that have evolved, antigenic variation is a particularly widespread reaction to thwart adaptive immunity. Though the reactions that underlie antigenic variation are highly varied, recombination by gene conversion is a widespread approach to immune survival in bacteri...
Origin recognition complex (ORC) architecture has only been explored in depth in the opisthokont supergroup of eukaryotes, which includes yeast and mammals, with little work in protists. The Kinetoplastida is a well-studied order of eukaryotic microbes and contains several important human parasites, such as Trypanosoma brucei. Genome sequencing of...
Initiation of DNA replication depends upon recognition of genomic sites, termed origins, by AAA+ ATPases. In prokaryotes a
single factor binds each origin, whereas in eukaryotes this role is played by a six-protein origin recognition complex (ORC).
Why eukaryotes evolved a multisubunit initiator, and the roles of each component, remains unclear. In...
Background
DNA replication initiates on defined genome sites, termed origins. Origin usage appears to follow common rules in the eukaryotic organisms examined to date: all chromosomes are replicated from multiple origins, which display variations in firing efficiency and are selected from a larger pool of potential origins. To ask if these features...
Eukaryotic genome duplication relies on origins of replication, distributed over multiple chromosomes, to initiate DNA replication. A recent genome-wide analysis of Trypanosoma brucei, the etiological agent of sleeping sickness, localized its replication origins to the boundaries of multigenic transcription units. To better understand genomic repli...
Nuclear DNA replication is, arguably, the central cellular process in eukaryotes, because it drives propagation of life and intersects with many other genome reactions. Perhaps surprisingly, our understanding of nuclear DNA replication in kinetoplastids was limited until a clutch of studies emerged recently, revealing new insight into both the mach...
Despite the efforts towards eradication, malaria remains the most deadly parasitic and vector-borne disease, urging for the development of an effective antimalarial vaccine. Recently, a renewed interest in Plasmodium attenuated whole-organism vaccine strategies has emerged, long acknowledged to experimentally induce full and sterile immunity agains...
Peptidomimetic imidazolidin-4-one derivatives of primaquine (imidazoquines) recently displayed in vitro activity against blood schizonts of a chloroquine-resistant strain of Plasmodium falciparum. Preliminary studies with a subset of such imidazoquines showed them to both block transmission of P. berghei malaria from mouse to mosquito and be highly...
Parasite infection can lead to alterations in the permeability of host plasma membranes. Presented here is the first demonstration that this phenomenon occurs in Plasmodium-infected liver cells. Using the whole-cell patch-clamp technique, volume-regulated anion channel (VRAC) activity was characterized in Huh-7 cells (a human hepatoma cell line) be...
Questions
Questions (9)
We are using myc-TRAP beads for IPs, and we are getting lots of unspecific bands. We were wondering if anyone has used a blocking step (with BSA or equivalent) when using these types of beads?
Thanks!
Hello,
I have data from an experiment in which I'm comparing cell cycle profiles (PI staining) in treated vs untreated cells. The problem was that in certain cases, the number of treated cells was rather low, so I wasn't able to acquire as many cells as in the untreated group. The differences are very clear by looking at the percentages (frequency of parent) of each cell cycle stage (different gates), but I'm quite concerned on how to represent the histograms overlayed. In flowJo, if you overlay the two histograms, it automatically scales the counts' y-axis; if selecting the option "relative to mode" this only changes the y-axis so to be a max of 100; if you select manual however, it plots the actual counts on the y-axis (which are different between my samples). I was wondering if anyone knows what would be the best way to represent this data as overlayed histograms, or whether it is more correct to actually represent them separately, side-by-side, with their actual y-axis counts, and percentage of the population per gate.
Thanks in advance.
