PHOSPHO-ENERGY TRANSFER

Cellular energy metabolism and actin-based cell dynamics

One line of research effort of the NCMLS Cell Biology Dept. that collaborates within the NCMD is aimed at the elucidation of the patho-physiology of Myotonic Dystrophy (DM1, a devastating trinucleotide expansion disorder that affects muscle, brain, endocrine systems, vision and cognitive and behavioural function). The protein products of the DMPK gene that is mutated in DM1 patients have a role in the regulation of mitochondrial physiology, Ca2+ ion homeostasis and actin remodelling.
In another line of research the group is studying the biological role significance of the creatine kinase (CK) and adenylate kinase (AK) circuits for transfer of cellular energy (~P). Isoform-members of the Creatine kinase and Adenylate kinase protein families function in mitochondria (in the inter-membrane or matrix space) and in the cytosol and provide ATP, the key metabolite of life, for actomyosin sliding in muscle cells and for actin remodelling and ion-homeostasis in neuronal tissues. Mouse and cell models with defect in the CK and AK pathways are studied to monitor cytoarchitectural adaptations and rewiring of metabolic pathways that occur in response to local or global energy crisis. Moreover, cell biological and reverse genetic approaches are used to study how in muscle, nerve and cancer cells the energy-metabolic state connects to cellular programming and viability control and to actin-based motility regulation. Research findings ultimately may be used for better diagnosis or the design of therapeutic modalities for a variety of health problems, including inheritable myopathies, ageing-associated neurodegeneration, or metastasis formation in cancer.

Contact
Name: Dr. Bé (Berend) Wieringa
Function: Professor of Cell Biology/Head Dept. Cell Biology
Department: 163 Cell Biology
Telephone number: +31 24 3614329/3614287
E-mail: B.Wieringa@ncmls.ru.nl
For details about the Dept. and Research see Web: http://www.ncmls.nl/celbio/index.html