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Sie sind hier: Startseite Forschung Prof. Dr. U. Schweizer

Forschung/Research

Ulrich Schweizer Prof. Dr. Ulrich Schweizer
Institut für Biochemie und Molekularbiologie
Nussallee 11, D-53115 Bonn
Tel. 0228-73 4444
Fax.0228-73 4558
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Research 

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Our research covers two principal areas of research: hormones and selenoproteins

In the field of thyroid hormone action and metabolism, we are interested in mechanism that regulate the availability of T3 in the cell before it can bind its nuclear receptor. Hence, we are interested in MCT8, a solute carrier protein, that helps thyroid hormones to cross the plasma membrane. Mutations in MCT8, lead to severe intellectual disability in patients. Another facet of pre-receptor regulation of thyroid hormone action pertains to local adjustment of T3 levels by the action of iodothyronine deiodinases, enzymes that are capable of activation and inactivation of thyroid hormones. We are interested in their structure and function. Deiodinases are selenium-containing proteins, which connects them with our second area of research.

Selenoproteins are proteins containing the rare amino acid selenocysteine (Sec). We are mainly interested in what selenoproteins are doing in the brain and how they are made. Since Sec is encoded by a UGA codon in the mRNA, a mechanism exists which prevents termination and favors elongation at the UGA/Sec codon. We are curious how this works and recently adopted the RiboSeq method in order to study the process more precisely.

Neurobiochemistry of Selenium:

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The complete article can be downloaded as PDF.

Thyroid hormone transport and metabolism

We have initially studied the biochemical properties of MCT8 as a thyroid hormone transporter in order to understand its structure and function. In parallel we worked on the function of Mct8 in the brain using a mouse model. Then, we found that commonly used drugs can interfere with the activity of MCT8 explaining previously puzzling clinical findings.

More recently, we are exploring the possibility to activate pathogenic MCT8 mutants using the chemical chaperone phenylbutyrate. The idea is that the drug (which can be used in humans) can restore the function of the transporter and hopefully alleviate the phenotype of patients. We have started in cell cultures, moved to iPS cells, and are now analyzing mouse models. 

The mechanism of deiodinases proved a scientific problem over decades. These enzymes are present only in vertebrates and resemble peroxiredoxins, which gives a hint to their evolutionary history. In collaboration, we have solved the partial structure of mouse Dio3. Now we want to see the full structures of all deiodinases and understand their molecular mechanism.

Funding:

We receive(d) funding from the DFG (Einzelanträge, Schwerpunktprogramm 1087, SFB 665/A7, Graduate College 1208, Schwerpunktprogramm THYROID TRANS ACT, Sherman Foundation, German Israeli Fund).

 

 

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