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Introduction Our laboratory is situated at the ground floor of building 6
(Biochemistry building) of HPI. Two additional floors are currently
being constructed above the existing building for the expansion of our
lab, funded exclusively by the lab’s budget.
Our main activities include:
a. The
study of the structure and function of nicotinic acetylcholine receptors
(AChRs) which are implicated in several severe neurological diseases.
b. The
study of myasthenia gravis (MG), which is usually caused by anti-AChR
autoantibodies, and the development of a specific therapy for this
disease.
c.
Investigation of the pathogenic role of another two membrane proteins,
MuSK and aquaporin-4, in the autoimmune neurological diseases MG and
neuromyelitis optica (NMO).
d. Very sensitive immunochemical diagnosis for three autoimmune neurological diseases (MG, NMO and LEMS).
e.
Services to the scientific community (e.g. monoclonal antibodies, mass
production of recombinant proteins by a high-tech bioreactor, protein
crystallization by a robot, DLS, etc) and support to the Greek MG
Association.
The expansion of our lab by the two additional floors will include,
amongst others, a dedicated place (clean room) for the development of
immunoadsorption columns under GMP standards necessary for the clinical
trials for MG therapy, a crystallization room for structural studies,
appropriate rooms for the further development of improved diagnostics
for neurological diseases and for the research on these diseases.
Additionally, the expanded laboratory will accommodate the
administrative activities of the Hellenic Myasthenia Gravis Association
(H-MGA).
Nicotinic Acetylcholine Receptors (AChRs)
Our laboratory is mainly studying the structure of the human nicotinic
acetylcholine receptors (AChR) and their role in several related
neurological diseases. AChRs are a family of membrane proteins located
in a number of synapses, either in the nervous system (central and
peripheral) or in the neuromuscular junctions mediating neuromuscular
transmission. AChRs are involved in several diseases, such as myasthenia
gravis (MG) and myasthenic syndromes (muscle type AChRs), Alzheimer’s
disease, Parkinson’s disease and schizophrenia as well as the addiction
to smoking (neuronal AChRs). Their importance in physiology and
pathology and the fact that they have been extensively studied renders
the AChRs as model neurotransmitter receptor molecules.
Muscle AChR and MG. The skeletal muscle AChR, consisting of 5
subunits (αβγαδ or αβεαδ), is fundamental for the neuromuscular
transmission. In MG, patients produce autoantibodies, which destroy the
AChRs at the neuromuscular junctions, resulting in muscular weakness and
fatigability. As the number of diagnosed patients increases, there is a
need for the development of improved and specific therapeutic
approaches for MG. Our studies involve mainly the thorough understanding
of the antigenic structure of muscle AChR, the pathogenic mechanisms in
MG, efforts to develop novel immunospecific therapeutic approaches and
the better diagnosis of the disease. The therapeutic approach which is
being developed by our lab focuses on the use of recombinant AChR
fragments with correct conformation as immunoadsorbents of patients’
antibodies.
Neuronal nicotinic AChRs. Neuronal AChRs are very
heterogeneous. They are also pentameric proteins, each formed by 1-4
kinds of homologous subunits chosen from a pool of 9 alpha (α2-10) and 3
beta (β2-4) subunits. We have initiated studies on some of the most
important subunits for understanding their structure, function and
involvement in pathology. To this aim we express the extracellular
domains of human neuronal subunits in eukaryotic expression systems, we
produce monoclonal antibodies against them and we study their structural
and biological properties. |