Protein design to generate bio-functional nanostru.. (Bionanotools)
Protein design to generate bio-functional nanostructures
Start date: Jul 1, 2010,
End date: Jun 30, 2014
The main objective of my research project is to understand how the structure and function of proteins are defined by their sequence and to apply learned rules to design new protein-based nanotools. In particular, I will focus on a type of proteins called tetratricopeptide repeats (TPR). They present a simple modular structure, where a small structural unit is repeated in tandem. Overall TPR domains are a very robust system to study protein structure, folding, and function, and to use them as building blocks for protein engineering to generate new functional nano-molecules. I aim to study natural TPR domains that mediate protein-protein interactions at a molecular level, and extract basic principles that govern these interactions to apply them in the design of TPR units with desired specific activities. I will also perform basic studies on protein stability and folding of designed TPRs to gain a better understanding on how the protein sequence determines thermodynamic stability. These studies will allow us to generate more stable proteins that will be useful in biotechnological applications, such as generation of novel biomaterials. The ability to discriminate between residues that determine the structure and stability, from those responsible of the binding specificity in the protein scaffolds, together with the capacity to generate super-stable scaffolds, opens the door to the generation of protein libraries. In such libraries only the binding sites will be randomized in order to incorporate a wide variety of potential specificities, and will be screened against different targets of interest using high-throughput methods. We will design functional proteins with defined binding-specificities and structural properties. These novel bio-tools will be extremely useful to monitor and investigate biological processes in vivo, as biosensors for diagnosis to detect disease biomarkers, and also as building blocks for applications in biomaterials design.
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