Richard McCulloch

Replication-stress response shapes Leishmania genome plasticity through non-equivalent RAD9 and HUS1 functions.

This study shows that HUS1 and RAD9 subunits of the 9-1-1 checkpoint clamp have opposing roles in shaping genome plasticity in Leishmania major through distinct replication-stress responses and genome remodelling patterns.

Single-cell transcriptomics reveals life cycle and cell cycle gene expression dynamics during in vitro growth of two Leishmania species

This study uses single-cell transcriptomics to analyze life cycle and cell cycle gene expression dynamics in two Leishmania species during in vitro growth, revealing developmental endpoints and cell cycle-related gene expression patterns.

De novo assembly of the Trypanosoma congolense genome reveals an organisation influenced by antigenic variation but distinct from Trypanosoma brucei

This paper presents a telomere-telomere genome assembly of Trypanosoma congolense, revealing distinct VSG organization and expression mechanisms compared to Trypanosoma brucei.

Trypanosoma congolense Variant Surface Glycoprotein gene expression occurs in the absence of monoallelic transcription control

This study shows that Trypanosoma congolense expresses multiple Variant Surface Glycoprotein genes in single cells, unlike Trypanosoma brucei, which uses monoallelic transcription.

Restricted expression site use and extreme genome diversification drives trypanosome antigenic variation in chronic bovine infections

The paper analyzes antigenic variation in Trypanosoma brucei during chronic bovine infections, revealing enhanced diversity and a reproducible temporal expression hierarchy of VSGs.

Reduced levels of inositol hexakisphosphate kinase (IP6K) impair life-cycle transitions and the intracellular development of Trypanosoma cruzi within human cardiomyocytes

This study shows that reducing IP6K levels in T. cruzi impairs key life-cycle transitions and intracellular development in human cardiomyocytes, suggesting IP6K as a potential drug target for Chagas disease.

DNA damage drives antigen diversification through mosaic VSG formation in Trypanosoma brucei

The paper demonstrates that DNA damage induces VSG recombination in T. brucei, leading to antigenic variation and immune evasion.

ATR, a DNA damage kinase, modulates DNA replication timing in Leishmania major.

This study shows that ATR modulates DNA replication timing in Leishmania major, promoting genome stability by preventing replication stress-induced chromosome instability.

Nuclear DNA replication in Leishmania major relies on a single constitutive origin per chromosome supplemented by thousands of stochastic initiation events

TrAGEDy: Trajectory Alignment of Gene Expression Dynamics

TrAGEDy aligns gene expression trajectories from different biological processes without integration, improving detection of biologically relevant genes in T cells and Trypanosoma brucei.

R-loops acted on by RNase H1 are a determinant of chromosome length-associated DNA replication timing and genome stability in Leishmania

This study shows that R-loops and RNase H1 regulate DNA replication timing and genome stability in Leishmania, linking R-loop homeostasis to chromosome size and replication order.

Nanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma brucei

This study uses Nanopore sequencing to show that DNA replication compartmentalization in Trypanosoma brucei affects genome stability and instability by influencing VSG gene recombination and chromosome stability.

AUK3 is required for faithful nuclear segregation in the bloodstream form of Trypanosoma brucei

This study shows TbAUK3 is essential for proper nuclear segregation and DNA stability in Trypanosoma brucei, with depletion causing segregation defects and increased DNA instability.

Genome-wide mapping of RPA1 and RAD9 reveals the management of polycistronic transcription, replication initiation, and responses to replication stress in Leishmania

This study maps RPA1 and RAD9 in Leishmania to understand replication stress response, showing stress hotspots correlate with replication initiation and transcription termination.

Aneuploidies are an ancestral feature of trypanosomatids, and an ancient chromosome duplication is maintained in extant species

The paper analyzes aneuploidy patterns across 866 Trypanosomatid isolates, finding aneuploidies are ancestral and an ancient duplication is maintained in some species.

RAD50 promotes DNA repair by homologous recombination and restrains antigenic variation in African trypanosomes

This study shows RAD50 promotes homologous recombination and limits antigenic variation in Trypanosoma brucei by controlling DNA repair mechanisms.

Transcription activity contributes to the firing of non-constitutive origins in Trypanosoma brucei

The paper shows that transcription activity triggers non-constitutive origins in Trypanosoma brucei to ensure timely DNA replication.

Application of long read sequencing to determine expressed antigen diversity in Trypanosoma brucei infections

This study uses long-read sequencing to analyze VSG diversity in T. brucei infections, revealing higher expressed diversity and early mosaic gene formation than previously observed.

Genome-wide mapping reveals conserved and diverged R-loop activities in the unusual genetic landscape of the African trypanosome genome

The paper maps R-loop activities across the genome of Trypanosoma brucei, revealing conserved and novel roles in transcription and genome dynamics.

The ATR kinase of Trypanosoma brucei links DNA damage signalling and monoallelic control of surface antigen gene expression during antigenic variation

This study shows that ATR kinase in Trypanosoma brucei is essential for DNA damage signaling and controls monoallelic VSG expression during antigenic variation.