Biochemistry professor receives funding to research rare neurodevelopmental condition

Professor Maolin Guo (Chemistry & Biochemistry) received a $150,000 grant from the Orphan Disease Center and Loulou Foundation to study CDKL5 disorder

Professor Maolin Guo standing at lectern

Professor Maolin Guo (Chemistry & Biochemistry) received a $150,000 grant from the Orphan Disease Center and Loulou Foundation for his project “Incorporation of functional unnatural amino acids into CDKL5 to study its function in cells”.

The project will investigate CDKL5 disorder. This rare neurodevelopmental condition caused by mutations in the cyclin-dependent kinase-like 5 (CDKL5) protein plays a critical role in brain development and function. However, the functions of CDKL5 and its pathogenic variants are still poorly understood. Guo’s project proposes to use a chemical biology approach to incorporate an unnatural fluorescent amino acid into CDKL5, and several of its pathogenic variants, to study their expression, subcellular location, trafficking, and dynamics in live human cells.

Moreover, photoreactive amino acids will be incorporated into CDKL5 to capture their interacting/binding partners in cells via photo-induced crosslinking. The in cellulo binding of CDKL5, and several pathogenic variants, with HDAC4 and MeCP2 will be tested to elucidate whether a missense mutation at the catalytic domain, a frame shift mutation, or a truncation nonsense mutation affects CDKL5 binding to HDAC4 or MeCP2.

The grant was funded by the Orphan Disease Center and Loulou Foundation. The Orphan Disease Center is based out of the University of Pennsylvania and, according to its website, develops transformative therapies using platform technologies that can be deployed across multiple rare diseases and emphasizes disorders with substantial unmet need independent of their incidence and will strive to assure access to patients of all populations. The Loulou Foundation is a private non-profit UK foundation dedicated to advancing research into the understanding and development of therapeutics for CDKL5 deficiency disorder. The Foundation has already funded important research projects at leading universities in the US and Europe, with 31 separate projects in 41 labs at 30 different institutions so far, enabling the focused research of over 120 scientists.

Guo believes his study will provide novel tools to better understand CDKL5 function in physiological and pathophysiological processes, which may aid the identification of novel therapeutic strategies.

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