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Master’s Thesis: Receptor-Ligand Interactions - Sweden
Posted on : 03 June 2017
Master’s Thesis: Mutational mapping of newly discovered receptor-ligand interaction
- Our company is an international specialty healthcare company dedicated to rare diseases.
- Our mission is to develop and deliver innovative therapies and services to improve the lives of patients.
- The product portfolio is primarily focused on Haemophilia, Inflammation and Genetic diseases
- We also market a portfolio of specialty and rare disease products for partner companies across Europe, the Middle East, North Africa and Russia.
- Our company is a pioneer in biotechnology with world-class capabilities in protein biochemistry and biologic manufacturing.
- Non-covalent interactions between proteins are critical in biological systems sustaining life.
- Multiple complex networks of reversible interactions between proteins have evolved and now make up essential mechanisms such as regulation of cellular growth and survival by intracellular networks, and immune response activation by a large range of secreted signaling factors, of which many are continuously being discovered and examined.
- Interactions involved in the immune system are especially important for drug discovery aimed at treating inflammatory or infectious diseases.
- Understanding these mechanisms is essential to accurate diagnosis and treatment of complicated disease implications.
- Signaling mechanisms can be challenging to elucidate in vitro due to the involvement of multiple binding partners or low binding affinities in these interactions. Nevertheless, information regarding binding affinity and which domains or amino acids are involved in the binding are highly valuable in order to design and engineer drugs aimed at modulating the signaling mechanism in question.
- Crystal structures of proteins reveal invaluable information regarding the nature of proteins and their functions.
- However, structures can be difficult and time-consuming to solve accurately, especially complexes of several interacting proteins.
- In addition, they reveal limited information regarding the dynamics of a protein-protein interaction.
- Methods in protein engineering such as site-directed mutagenesis coupled with in vitro binding assays are powerful tools to examine protein-protein interactions in order to gain information regarding which amino acids are most important for establishing a stable interaction between a pair of binding proteins.
- The aim of this diploma work is to map the interaction between a poorly understood receptor-ligand pair known to be involved in acute inflammation.
- Protein variants with reduced, or indeed increased, binding affinity can be discovered by mutating amino acids one-by-one or together in a combinatorial library.
- This can be used to guide further engineering efforts and drug design.
- Master student in molecular biology, protein engineering or related field
- Experience and knowledge in one or several of the following skills:
- Sub-cloning of recombinant genes
- Bacterial or mammalian protein expression
- Display technologies
- High-throughput screening
- Protein characterization (ELISA, SDS-PAGE, western blots, MS)