Addressing the need for new antibiotics through underexplored bacterial targets

The group is involved in several research projects where novel targets for future antibiotics are investigated. There is an urgent need for new antibiotics to prevent the looming crisis of antimicrobial resistance. Antibiotics are a prerequisite for modern medicine, and the WHO has published a list of bacteria for which antibiotics are in high demand and urged that research and drug discovery efforts are directed toward these. To tackle this crisis, we need fundamental knowledge on new targets for antibiotics, and we need compounds that can get into bacteria and work on these targets.

In our work, we are contributing to addressing the global AMR crisis by making molecules that can interfere with processes that are essential in bacteria. Specifically, we are addressing several different riboswitches, which are non-coding structural elements in mRNA that regulate gene expression by binding small molecules, through design and synthesis of ligands for these. In addition, we are targeting three enzymes that are important for bacterial fatty acid synthesis through design and synthesis of inhibitors.

Read more (under construction).

Early drug discovery

We are involved in several research projects where we are aiming to discovery molecules that can be the starting points for drug discovery endeavours. The group is partner in the RESPOND3 project on responsible early digital drug discovery within the Centre for Digital Life Norway. This project focuses on developing better computational approaches and responsible innovation strategies in early drug discovery with applications to antibiotics and inflammatory lung diseases.

Inhibitors of N-terminal acetyl transferases

Proteins constitute an essential part of the machinery of life and display enormous variation in both structure and function. In addition to the diversity inferred by the 20 coded amino acids, proteins are often covalently modified during or after biosynthesis, which adds additional layers of complexity.

Acetylation is one of the most common co- or post-translational protein modifications, and occurs either on the amino group of lysine side chains (K-acetylation) or on the alpha-amino group of N-terminal residues (Nt-acetylation).

Nt-acetylation of proteins is extremely common and occurs on more than 80% of all human proteins. Biochemically it consists of transfer of an acetyl group from acetyl coenzyme A (Ac-CoA) to the protein substrate and is catalysed by the N-terminal acetyltransferase (NAT) group of enzymes.

Although our understanding of the NATs has increased in recent years, there are fundamental questions that remain unanswered in the field:
– What are the cellular roles of NAT enzymes (and thus Nt-acetylation)?
– Can NATs be targeted for therapeutic intervention in cancer and other diseases?

Access to specific and potent NAT inhibitors is a prerequisite to answer these questions, and we are working toward equipping the scientific community with these molecular tools.

Molecular imaging

We are working on developing new methods for radiolabeling of peptides and peptide-based probes for PET-imaging and are part of the Tracer Development Center of the Norwegian Nuclear Medicine Consortium. We are also working on the development of new probes for optical imaging and new applications for these.