Skip to content
Le Roch Lab
Blood smear showing Plasmodium parasites at multiple developmental stages

Research

Chromatin & Gene Regulation

The question

A genome that is read by how it is folded.

Deciphering the role of epigenetics and chromatin structure in gene regulation and virulence — probed with next-generation sequencing, nucleosome mapping and histone analysis.

The malaria parasite runs a tightly timed developmental programme with an unusually small set of sequence-specific transcription factors. Much of the control appears to sit above the sequence itself: in how the genome is packaged into nucleosomes, which histone marks it carries, and how the chromosomes fold inside the nucleus.

We measure that packaging directly — nucleosome positioning, histone modification, DNA methylation and three-dimensional genome architecture — then ask which of those features predict when a gene switches on. Our 3D models showed virulence gene families clustering in a repressive compartment at the nuclear periphery. More recent work has moved from description to mechanism: identifying the proteins and long non-coding RNAs (lncRNAs) bound to chromatin, and testing what happens when they are removed.

Hi-C contact map above aligned chromatin coverage, histone occupancy and gene-annotation tracks
Hi-C contact map with aligned chromatin accessibility, histone occupancy and gene-annotation tracks — the folded genome and the marks it carries, measured together.

How we look

Techniques used in this area

Chromatin & epigenome

  • ChIP-seq
  • CUT&Tag
  • Hi-C
  • BS-seq
  • MeDIP-seq
  • MNase-seq

Nucleosome positioning, histone modification, DNA methylation and chromosome folding — each measured genome-wide, then aligned against transcription.

Readout & validation

  • RNA-seq
  • Proteomics
  • MudPIT mass spectrometry
  • CRISPR

Platforms

  • Illumina
  • Oxford Nanopore
  • PacBio
eLife
eLife2025

A drug repurposing approach reveals targetable epigenetic pathways in Plasmodium vivax hypnozoites

Maher SP, Bakowski MA, Vantaux A, Flannery EL, Andolina C, Gupta M, Antonova-Koch Y, Argomaniz M, Cabrera-Mora M, Campo B, Chao AT, Chatterjee AK, Cheng WT, Chuenchob V, Cooper CA, Cottier K, Galinski MR, Harupa-Chung A, Ji H, Joseph SB, Lenz T, Lonardi S, Matheson J, Mikolajczak SA, Moeller T, Orban A, Padín-Irizarry V, Pan K, Péneau J, Prudhomme J, Roesch C, Ruberto A, Sabnis SS, Saney CL, Sattabongkot J, Sereshki S, Suriyakan S, Ubalee R, Wang Y, Wasisakun P, Yin J, Popovici J, McNamara CW, Joyner C, Nosten FH, Witkowski B, Le Roch KG, Kyle DE