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Project wants to understand regulation of CLCA1 to shed light on its role in airway disease

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Elisabeth Nyström is a postdoctor at the Department of Medical Biochemistry and Cell Biology at Sahlgrenska Academy and is one of this year's recipients of the Bollan Scholarship. Elisabeth tells us about her project and the work she will be doing at Core Facilities.

Can you give us a summary of your research project?

Mucus accumulation in the airways is commonly seen in patients with chronic obstructive pulmonary disease (COPD) and certain types of asthma and contributes to the disease by restricting airflow and increasing the risk of bacterial infection. Strong induction of the protein calcium-activated chloride channel regulator 1 (CLCA1) has been correlated with mucus accumulation in previous research but the functional role of this protein in COPD and asthma remains largely unknown. My research is focused on characterizing the function of CLCA1, primarily in the intestinal mucus where it is normally expressed. Here we have found that CLCA1 acts as a proteolytic enzyme that can cleave the main mucus protein Mucin-2 (Muc2) and thereby affects mucus properties. In the proposed project I will investigate how the enzymatic activity of CLCA1 is regulated in more detail; A common pathway of protease activation is proteolytic cleavage of the protease. I will thus investigate if shorter versions of CLCA1 are more enzymatically active and I will also characterize the biochemical properties of these shorter versions. I hope that shedding light on these questions will help us understand the role of CLCA1 in airway disease and aid the development of drugs to facilitate mucus clearance.

Why did you apply to the Bollan-scholarship?

The Bollan-scholarship gives a great opportunity for young researchers to fund certain aspects of their projects. The Core Facilities provide an excellent platform to get expert help to accelerate projects without having to learn or set up techniques from scratch.

You are going to work with Mammalian Protein Expression at Core Facilities, what are you hoping to achieve working with their infrastructure?

The protein I’m working with is both large and complex, with several disulphide bonds and glycosylation. Thus, it can only be expressed in mammalian cells to produce high-quality products. MPE has great facilities to produce large quantities of mammalian proteins, which is hard to achieve without a specialized lab, and they also aid in protein purification which frees up time for me. Also, as they are local at the Sahlgrenska Academy it is very easy to have an efficient dialog, in contrast to working with external companies. Thus, I hope to get large amounts of protein of good quality for downstream work.

From a research quality point of view, what value are you hoping to get using Core Facilities?

By using MPE I know that the protein is expressed in cells suitable for this type of protein production and that the product I get in the end is of high quality in respect of production. MPE and the other infrastructures at Core Facilities provide state-of-the-art equipment that is not directly available for individual labs and thus ensure that projects are executed in an up-to-date praxis.