Universiteit Leiden

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Macromolecular Biochemistry


Research projects for students of the University of Leiden and other Dutch Universities are often available at the MacBio group. The research lines are also described in the Research section. For details of specific projects contact the principal investigator (Ubbink, Dame).

Protein Interactions: Enzymes and complexes

Supervisor: Marcellus Ubbink
Duration: Variable

The research of Prof. Ubbink is aimed at understanding how proteins really work at the atomic level. Analysis of protein structure and dynamics are combined with functional studies. Two lines can be distinguished: protein complexes and enzymology.

 Protein complexes are studied to understand how weak and transient interactions occur. Proteins often form such weak complexes, for example to transfer electrons (in respiration, photosynthesis, etc.) or in intracellular signaling cascades. NMR spectroscopy is a very useful tool to study the biophysical details of the interactions, such as the roles of electrostatic and hydrophobic forces in the formation and dissociation of complexes.

The second line of research is aimed at understanding enzymes that are important for human health. For example, the evolutionary combat between beta-lactamases and beta-lactam antibiotics is studied. Mutagenesis, kinetics, crystallography and NMR are used to characterize these interactions, with the ultimate aim to develop inhibitors that are no longer prone to induce evasive evolution of the lactamase enzyme.

Student projects generally involve protein production using recombinant expression systems and protein purification. Then, various biophysical measurements are performed to characterize the protein and its interactions at the atomic level. The analysis of such data requires a certain interest in quantitative experiments and computer work.

Molecular basis of genome organization and activity

Supervisor: Remus Dame
Durarion: Variable

Research in the group of Dr. Dame is focused on understanding the mechanisms by which chromatin is structured and functionally organized in bacteria and archaea. Transcription of genes occurs in a chromatin context and extensive interplay exists between genome structure and genome activity. Moreover, genome folding is affected by changes in cellular growth conditions and these changes are translated in altered gene expression and cellular behavior.

Genome organization across the three domains of life appears different, but upon closer inspection it becomes clear that many principles are shared. The group aims at determining fundamental principles of organization and to determine evolutionary relationships.

In order to be able to mechanistically dissect and understand these processes the group applies an extensive toolbox of techniques ranging from molecular genetics, conventional and single-molecule biochemistry to life cell microscopy and other state-of-the art in vivo approaches.

Internships are typically connected to projects currently running within the group. In terms of techniques, projects are generally tailored depending on the interests and capacities of the candidate.