Somatic adaptation and sex differences in human endocrine development and disease (360G-Wellcome-209328_Z_17_Z)
<p>Our work focusses on new genetic mechanisms affecting human adrenal and reproductive function. We have recently described a multisystem growth restriction disorder caused by gain-of-function of SAMD9, where somatic adaptation can modify phenotype and mask detection of the genotype. In parallel, we developed a transcriptomic atlas of human adrenal and gonad development, mapping out sex-specific effects of organogenesis. We now plan to develop these insights to address several related fundamental questions:</p> <p>1) How extensive is SAMD9 variability in endocrine and growth phenotypes and does dynamic somatic adaptation play a wider role in human disease mechanisms;</p> <p>2) What are the dynamic roles of sex chromosomes and sex hormones in development (focussing on brain, adrenal gland and genital tubercle), and how does genetic variability of the X-chromosome contribute to phenotype in Turner syndrome (45,X);</p> <p>3) Can we apply these concepts to discover new genetic mechanisms underlying adrenal and reproductive disorders.</p> <p>This work would provide novel disease models and approaches to analysis, could link the dynamics of development and sex-differences to common conditions (e.g. neurodevelopment, stress, early-onset hypertension), and would continue to elucidate the causes of human adrenal and reproductive disorders, with important implications for personalised management and development of new therapies.</p>
£1,561,134 28 Nov 2017
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Amount Awarded | 1561134 |
Applicant Surname | Achermann |
Approval Committee | Science Interview Panel |
Award Date | 2017-11-28T00:00:00+00:00 |
Financial Year | 2017/18 |
Grant Programme: Title | Senior Research Fellowship Clinical Renewal |
Internal ID | 209328/Z/17/Z |
Lead Applicant | Prof John Achermann |
Planned Dates: End Date | 2023-02-01T00:00:00+00:00 |
Planned Dates: Start Date | 2018-02-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |
Sponsor(s) | Prof Rosalind Smyth |