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The aim of this studentship is to unravel the role of calcyclin in Annexin A11 mediated ALS by studying specific Annexin A11 mutations in-vitro and in-vivo to determine disease mechanisms.A secondary goal is to determine the broader role of calcyclin in ALS pathogenesis.
The underlying genetic architecture of the disorder is broad and exome sequencing of familial ALS samples (found in approximately 10% of total cases) has successfully identified six new ALS genes over the last five years eg. Our group has recently identified another novel ALS gene, ANXA11 (recently published in Sci Transl Med. Annexin A11 (encoded by ANXA11) is a phospholipid and calcium binding protein, in which ALS mutations form insoluble aggregates in-vitro and in post-mortem tissue that also abolish binding to calcyclin.
The average Cp G methylation in this region was 27.0%, 19.5%, and 15.6% for liver, heart and lung tissues respectively.
In all tissues analyzed a methylated region was observed immediately prior to the transcription start site (−1355bp to −707bp, relative to ATG).
Based in Cranbury, New Jersey, Amicus Therapeutics (NASDAQ: FOLD), a biotechnology at the forefront of individualized medicine, is focusing on the development of a novel chaperone therapeutic - that either stabilizes a defective protein by itself or in combination with existing enzyme replacement therapies ("ERTs").
Promising prospects of the combinations of chaperone pharmacologic plus novel ERT lend support to bullish claims.
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For n-type host the Sn substitution is more preferable than Pb-$\Box$ formation, while for p-type host the trend is exactly opposite.