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Protein aggregation: catching the first steps

Protein aggregation: catching the first steps

Many diseases are associated with protein aggregation including Parkinson's and Alzheimer's disease. The aggregation process starts with a rare event, where multiple proteins meet and form a nucleus for aggregation. From this initial nucleus onwards aggregation is fast and almost unstoppable. Early intervention, at the state of the nucleus, is therefore the most promising option to prevent these diseases. However, there is little known about the formation of the aggregation nucleus. Here you will study the first steps in the protein aggregation process that lead to the formation of a nucleus.

Approach: You will use single molecule sensitive fluorescence microscopy to follow the aggregation process protein by protein. You will look at the speed (rates) at which aggregates form and disassemble and thus gain insight into the aggregate stability. Further we are interested in how these rates are influenced by other components including the presence of chaperones that help prevent aggregation or viruses and other factors that induce aggregation.

You will:

  1. Fluorescently label the relevant proteins
  2. Observe the protein aggregation either: on functionalized surfaces using TIRF microscopy or in solution using FCS/TCCD approaches
  3. Find ways to cleaverly detect rare events of interest in the recorded data

If you are interested, please feel free to contact us. Within the Nanobiophysics group we try to provide you with a BSc/MSc assignment that fits your expertise and interest.

 Please contact:

Mireille Claessens: m.m.a.e.claessens@utwente.nl, Zuidhorst 163

Christian Blum: c.blum@utwente.nl, Zuidhorst 168