Hans Heus

RNA and Biophysical Chemistry

Nucleic acids, RNA in particular are central to the molecular organisation and  regulation of cellular processes. Our aim is to understand the collective interplay of RNA molecules in complex environments using bottom-up and top-down approaches, covering a wide range of model systems from in vitro biomimetic systems to living cells. We use a broad multidisciplinary approach covering many molecular and chemical biology tools to prepare tailor-made samples and various advanced spectroscopic and microfluidic techniques to characterise biophysical properties important for life.

Aptamer technology and nucleic acid therapeutics
Aptamers are artificial RNA or DNA oligonucleotides that can be selected from large libraries to interact with small molecules, biopolymers, surfaces, or even whole cells and rival antibodies in affinity and specificity. We explore the usage of multivalent aptamer-polymers in breast cancer detection and treatment as well as in the context of leukemia and tumor escape.

Molecular crowding and confinement
In living cells confinement, molecular crowding and heterogeneity of local environments play a major role in the action of biomolecules, e.g., by affecting macromolecular reaction rates and equilibria. We investigate crowding and confinement effects on nucleic acids using hydrogels and molecular crowding agents to approach the complexity of living cells.

Paraspeckles: The role of membraneless organelles seeded by lncRNAs
Long noncoding RNAs (lncRNAs) have emerged as key regulators of gene expression. A subset of lncRNAs has specifically evolved to create sub-nuclear membraneless organelles that function to concentrate specific RNAs and proteins for cellular maintenance, development and stress control. Paraspeckles, membraneless organelles seeded by the lncRNA NEAT1 - one of the most abundant lncRNAs in human cells - are among the most predominant membraneless organelles and have been associated with gene regulation in stress and cancer scenarios. We use NEAT1 paraspeckles as a model system for understanding how multivalent RNA and protein interactions drive formation of membraneless organelles by phase-phase separation and to investigate the potential of paraspeckle signatures in diagnosing cancer development and treatment.