Center for Advanced Drug Analysis

Analysis of the structure and dynamics of biopharmaceuticals

Analysis of the primary and higher-order structure of protein-based drugs is critical for both understanding molecular action as well as monitoring and comparing drug product quality.

In this suite of projects, you will apply a new powerful analytical technology that uses mass spectrometry to measure the hydrogen/deuterium exchange of proteins in solution (HDX-MS). By HDX-MS, we can obtain detailed information on the structure and dynamics of biopharmaceuticals.

You will use this technique to analyze and compare the structural properties of new potential protein drugs in development and thus help to achieve a molecular understanding of their pharmaceutical properties and function in the human body. Work will be done in close collaboration with researchers at UCPH or industrial collaborators such as Biogen Idec (USA), Roche (Germany) and Novo Nordisk (Denmark), depending on the project.

There is typically also the possibility to perform parts of the project at the industrial collaborator.

No. of students: 1-2

Understanding the binding of drugs to target proteins of the human body

HDX-MS is a very sensitive method to study the binding of small molecule ligands or large protein-based drugs to naturally occurring protein receptors in great detail. By performing HDX-MS of the protein receptor in the absence and presence of a single or a panel of potential ligands, we can map the binding site of ligands on the protein receptor and study the structural effects of binding. In this project, you will use  

HDX-MS to study both the binding of ligands (small molecule or large protein-based) to important new pharmacologically interesting protein receptors. Work will be conducted in collaboration with academic/industry collaborators and has the potential to be extended into a PhD project.

No. of students: 1-2

Coupling microfluidics and mass spectrometry for improved analysis of proteins

MS analysis of proteins requires specialized sample treatment and advanced analytical techniques as they are large and complex and often contain modifications (e.g. glycosylations, disulfide bonds). We are exploring the use of microfluidic chips to perform rapid and automated preparation of protein samples for MS analysis. You will learn how to implement protein chemistry and sample processing on a microfluidic chip coupled to MS.

The project is supported by a large grant to the group from the EU (ERC Consolidator Grant) and has the potential to be extended into a PhD project.

No. of students: 1-2

Understanding the functional impact of engineered oligomeric antibodies

Immunoglobulins, also known as antibodies, are an important class of proteins frequently used as biotherapeutics. In the body, immunoglobulins can be found as several types and subclasses.

Some of these immunoglobulin subtypes can form multivalent structures, meaning they contain several copies of the same amino acid sequence that bind a target of interest.

In this project you will use both native MS and HDX-MS to characterize how the level of multivalency found in recombinant immunoglobulins affects their structure, dynamics, and potency in the context of designing more effective biotherapies.

No. of students: 1-2