Open projects at Department of Chemistry

• Metal-ion catalyzed oxidation and reactive oxygen species
• Structure and function of redox-active metalloenzymes
• Labeled proteins, peptides, DNA, and RNA

The Bjerrum Group focuses on unraveling the role of metal ions in biological systems at a molecular level. Their research aims to deepen the understanding of chemical processes, mechanisms, and dynamic interactions that occur between metal ions, biomolecules, RNA/DNA and proteins. These insights have significant implications for metabolic and biotechnological processes.

Professor Anders Lund:

• Cancer biology with emphasis on senescence and translational control
• Non-coding RNA
• Ribosome biology

The Lund Group investigates ribosomes, the molecular machines responsible for decoding genetic information to synthesize proteins. Their primary goal is to identify ribosome subtypes, analyze their unique compositions, and understand how these subtypes enable selective mRNA translation. This research offers insights into cancer biology and regulation of gene expression.

Associate Professor Peter Waaben Thulstrup:

• Biomolecular structure and function through advanced spectroscopic investigations (e.g., fluorescence, CD, MS, NMR and more.)
• Labeled proteins, peptides, DNA, and RNA

The Thulstrup Group employs spectroscopic and analytical techniques to study molecular structures, functions, and dynamics. With expertise in the biophysical characterization of peptides, proteins, and nucleic acids, their research explores the structural stability and dynamic behavior of biomolecules to gain insights into their functional roles.

• What?
  • The PhD project aims to elucidate the structural and chemical mechanisms underlying metal-ion catalyzed oxidative RNA modifications. RNA’s single-stranded nature makes it more susceptible to oxidative damage than DNA, yet this area remains underexplored. The study will investigate the effects of metal-ion catalyzed oxidation (MCO) on synthetic RNA sequences (20–50 nucleotides) to enhance understanding of RNA stability and the types of oxidative damage that occur. Additionally, the project will assess the protective effects of antioxidants on RNA.
• Collaboration with the Lund group will extend the research to biological contexts, focusing on how oxidative RNA modifications might alter ribosome function and impact cell fate decisions.
• How?
  • Production and characterization of reactive oxygen species (ROS) under near-physiological conditions (optimized concentrations, buffers, pH, etc.)
    • Identification and characterization of oxidative modifications in synthetic single- and double-stranded RNA sequences using advanced analytical techniques:
      • High-resolution ESI TOF-MS
      • NMR spectroscopy
    • Structural assessments of modified RNA
    • Biological investigations into how oxidative RNA modifications affect ribosome translation, in collaboration with the Lund group.
• Why?
  • This project will:

1. Advance understanding of RNA oxidation, contributing to nucleic acid chemistry.
2. Address challenges in RNA nanotechnology by overcoming oxidation-related stability issues.
3. Explore the role of RNA oxidation in disease, particularly its potential impact on protein synthesis and cell fate.

The project bridges chemistry and biology, integrating insights into metal-ion chemistry, RNA biology, and ribosome function. The project involves aspects of human cell biology (RNA biology) and chemistry. Collaboration with Professor Anders Lund’s group will provide expertise in DNA/RNA and ribosome biology, extending the research's relevance to various biological systems and diseases. Well-defined RNA oxidations, obtained in the Bjerrum group, will be analyzed in the Lund group using nanopore sequencing and ribosome translation studies to determine if these oxidation sites hold biological significance. The project will be realized through a close interplay between the research environments and the team members, contributing their expertise in different areas of the project.

• https://chem.ku.dk/research_sections/nanochem/jc-group/ 
• We focus on the functions and underlying photophysical properties of fluorescent molecular and semiconductor nanomaterials, with particular interests to their bioimaging applications. We are developing ultrabright fluorescent nanoparticles based on a molecular self-assembly approach. Using ultrafast optical spectroscopy with femtosecond time resolution, we uncover their critical photophysical processes, provide in-depth insights that guide the development of new, high-performance fluorescent nanoparticles.

• https://www.cancer.dk/danish-cancer-institute/research-groups/cellular-homeostasis-and-recycling/ 
• The group focuses on autophagy, a conserved and essential cellular quality control pathway. We study how the process works at a mechanistic level, how it contributes to disease including cancer initiation and progression as well as how its manipulation can alter therapeutic outcomes. We apply a broad portfolio of techniques spanning across several types of microscopy, RNA sequencing, proteomics, advanced biochemistry and high-content image-based screening.

• Visualizing the location of proteins and RNAs at subcelluar level is critical for investigating the causes and mechanisms of diseases including cancer initiation and progression as well as how their manipulation can alter therapeutic outcomes. However, many important proteins and RNAs, related to diseases, have a low ambandance. It is challenging to visualize them at subcellular level with conventional fluorescent markers. In this project we aim at using our newly developed ultra-bright organic fluorescenet nanoparticles, based on a molecular self-assembly approach, called: Small‐Molecule Ionic Isolation Lattices (SMILES), for visualizing low abundant RNAs, and investigate their role at causing diseases. The SMILES nanoparticles are over 400 times brighter than conventional fluorescent markers. This exceptional brightness will allow us to visualize rare biological events that were previously undetectable, which will open new possibilities for advanced imaging in biological research.
• In this project, we will be developing and optimizing new SMILES nanoparticles with different emission colors across the whole visible spectral region and different fluorescent lifetime (nanosecond to microsecond) based on a fundamental understanding of their photophysics. Then, we will encapsulate the SMILES nanoparticles with biocompatable surface capping agents, which will ensure the nanoparticles are stable and biocompatable in pysological enviroment (e.g., cells, blood and tissues). Then the surface of the nanoparticles will be modified with functional molecules (three different types of functional molecules: single strand DNAs, antibodies, nanobodies) via click chemistry, which will ensure their selective targeting proteins, and RNAs. We will utilize surface-modified SMILES nanoparticles conjugated with antibodies and nanobodies to visualize proteins, and single-stranded DNA conjugated SMILES nanoparticles to visualize RNAs at the subcellular level using expansion microscopy.This will aid in answering important questions in regarding the subcellular distribution of single, low abundant RNA transcripts that are difficult to visualize using conventional RNA imaging technologies.

The project is related to fluorescent nanoparticles development, surface modification and cancer/disease mechanism study. In this project we aim to use ultra-bright SMILES nanoparticles to visualize low-abundant RNA transcripts (including both mRNAs and short/long ncRNAs) at subcellular level to reveal their molecular mechanisms for causing cancers. Development of these SMILES nanoparticles presents a promising opportunity to obtain high-resolution visual details that are not possible with conventional methods. The success of this project will be groundbreaking. Ultimately, this will help us to understand new aspects of how RNA homeostasis is controlled in stress response and cancer development and may provide valuable information on RNA stabilization strategies with potential therapeutic applications.This project will need an unusual cross-section of expertise to address this challenge: deep physical understanding of the photopysical processes in nanoparticles, to design and study the supramolecular organization of molecular materials at the nanoscale, to modify the surface of the nanoparticles with targeting molecules, to implement the nanoparticles to biomedical imaging setting. This includes imaging in cancer cells and tissues to obtain in depth information about subcellular localization and cellular/tissue uptake mechanisms. To meet these scientific and methodological challenges, both research groups bring key competences to the table:

Chen, is an expert in ultra-fast spectroscopy, time-resolved fluorescence spectroscopy, photophysics, and energy migration in fluorescence nanomaterials. He developed the first SMILES nanoparticles.

Frankel, is an expert in molecular and cellular cancer biology, subcellular RNA sequencing, cell-imaging, autophagy, cellular homeostasis and cellular stress response.