1. Centromere Identity

Every chromosome requires a centromere to ensure its accurate inheritance. Unlike most genomic features, centromeres are not defined solely by DNA sequence but by specialised chromatin and protein assemblies that are propagated across cell generations. Understanding how centromere identity is specified and maintained remains one of the central questions in chromosome biology. Our work combines structural biology, biochemistry, and cell biology to reveal how centromeric chromatin is assembled, recognised, and inherited. By studying these mechanisms across diverse organisms, we seek to uncover both conserved principles and evolutionary innovations that shape chromosome inheritance.

Research questions

  • How are centromeres established and maintained?
  • How is centromere identity inherited through cell division?
  • What molecular features distinguish centromeric chromatin from the rest of the genome?

Publications

1. Ali-Ahmad et al (2026). Structure and dynamics of 2x(CENP-A/H4)2 octasome reveal a possible intermediate in centromeric chromatin. Life Science Alliance. 

2. Gupta, Sekulić et al. (2025). Solution conformational differences between conventional and CENP-A nucleosomes are accentuated by reversible deformation under high pressure. Chromosome Res. 

3. Nagpal, Ali-Ahmad et al. (2023). CENP-A and CENP-B collaborate to create an open centromeric chromatin state. Nat Commun. 

4. Ali-Ahmad and Sekulić (2020). CENP-A nucleosome—a chromatin-embedded pedestal for the centromere: lessons learned from structural biology. Essays in Biochemistry.

5. Ali-Ahmad et al (2019). CENP-C unwraps the human CENP-A nucleosome through the H2A C-terminal tail. EMBO reports. 

6. Sekulic et al (2010). The structure of (CENP-A-H4)2 reveals physical features that mark centromeres. Nature. 

2. Chromosome Segregation Mechanisms

The centromere functions as a signalling hub that coordinates chromosome segregation during mitosis. Our work seeks to understand how the Chromosomal Passenger Complex is recruited to centromeres and how Aurora B kinase is activated to drive accurate chromosome segregation. By combining structural biology, biochemistry, and cell biology, we uncover the molecular mechanisms that ensure faithful chromosome inheritance.

Research questions

  • How is the Chromosomal Passenger Complex localized to centromeres?
  • How is Aurora B kinase activated during cell division?

Publications

1. Segura-Peña et al (2023). The structural basis of the multi-step allosteric activation of Aurora B kinase. eLife. 

3. Evolution of Chromosome Inheritance

Although all eukaryotes must faithfully segregate their chromosomes, the underlying molecular components have diversified dramatically during evolution. Building on our long-standing work on centromere structure and function, we are beginning to explore how chromosome inheritance systems evolve across species. Recent studies from the lab explore unexpected adaptations in Lepidoptera, including organisms that appear to have lost canonical centromere components, challenging traditional views of centromere organization. We are also establishing Atlantic cod as a new system for investigating centromere biology and chromosome inheritance in vertebrates. By integrating comparative genomics, structural biology, biochemistry, and emerging model organisms, we aim to uncover both conserved principles and evolutionary innovations that shape chromosome inheritance across evolutionary time.

Research questions

  • How do centromeres evolve?
  • How do different organisms solve the same chromosome inheritance problem?
  • What are the conserved principles of chromosome inheritance across eukaryotes?

Publications

1. Sankaranarayanan et al. (2025). Insects evolved a monomeric histone-fold domain in the CENP-T protein family. EMBO Rep. 

Methods and Collaborations

In addition to our own research programme, we collaborate extensively with investigators from different disciplines, providing expertise in structural biology, protein biochemistry, and biophysics.

Our laboratory has extensive experience in cryo-electron microscopy (cryoEM), hydrogen-deuterium exchange mass spectrometry (HDX-MS), protein modelling and integrative structural biology. Through national and international collaborations, these approaches are applied to diverse biological systems, including chromatin, genome stability, immunology, host-pathogen interactions, and protein regulation. We are particularly interested in collaborative projects that benefit from integrative structural and biophysical approaches.

Publications

1. Heggelund et al (2026). Cryo-EM structure of the complex between transglutaminase 2 and the 45 kDa domain of fibronectin. JBC. 

2. Timmer et al (2025). LRRC59 cooperates with nuclear transporters to restrain the nuclear envelope repair machinery and safeguard genome integrity. Nat Commun.

3. Petersson et al. (2025). Orally delivered toxin–binding protein protects against diarrhoea in a murine cholera model. Nat Commun. 

4. Dorraji et al (2022). Development of a High-Affinity Antibody against the Tumor-Specific and Hyperactive 611-p95HER2 Isoform. Cancers.