Research Awards
Matthew Tudor, Ph.D.
Whitehead Institute
Mentor: Rudolf Jaenisch
Genetic and molecular characterisation of the 3 MBD family members, MBD1, MBD2 and MeCP2
$100,000
Recipient of the Alan P. Wolffe Memorial Fellowship
Lay Progress Report (August 2005)
This post-doctoral fellowship was transferred from Matthew Tudor to Qiang Chang.
I have been using the Mecp2 mutant mice as model system to study the molecular mechanism of the Rett Syndrome (RTT). Our previous work has shown that the MeCP2 protein binds to the promoter of the BDNF gene (brain-derived-neurotrophic-factor) and can regulate its transcription in cultured neonatal neurons. However, it is not clear what role, if any, BDNF plays in vivo in RTT pathogenesis. In order to address this question, I have manipulated the level of BDNF in post-mitotic neurons in the postnatal brain in Mecp2 mutant mice in a temporally- and spatially-controlled manner. My results clearly show that overexpressing BDNF in the postnatal brain of Mecp2 mutant mice slows down RTT disease progression, whereas removing BDNF in the same neurons accelerates RTT disease progression. These results implicate BDNF and other components of the BDNF signaling pathway as potential candidates for treating RTT patients. In addition to studying the role of BDNF in RTT pathogenesis, I have been searching for more MeCP2 target genes. Research along this line will help us fully understand how mutations in the Mecp2 gene cause RTT. Moreover, in collaboration with the laboratory of Dr. Sacha Nelson at the Brandeis University, I have identified a specific electrophysiological defect in the somatosensory cortex of the Mecp2 mutant mice. This assay will be a valuable tool to study RTT at the synaptic level.
Matthew Tudor, Ph.D.Whitehead Institute
Mentor: Rudolf Jaenisch
Genetic and molecular characterisation of the 3 MBD family members, MBD1, MBD2 and MeCP2
$100,000
Recipient of the Alan P. Wolffe Memorial Fellowship
Lay Progress Report (August 2005)
This post-doctoral fellowship was transferred from Matthew Tudor to Qiang Chang.
I have been using the Mecp2 mutant mice as model system to study the molecular mechanism of the Rett Syndrome (RTT). Our previous work has shown that the MeCP2 protein binds to the promoter of the BDNF gene (brain-derived-neurotrophic-factor) and can regulate its transcription in cultured neonatal neurons. However, it is not clear what role, if any, BDNF plays in vivo in RTT pathogenesis. In order to address this question, I have manipulated the level of BDNF in post-mitotic neurons in the postnatal brain in Mecp2 mutant mice in a temporally- and spatially-controlled manner. My results clearly show that overexpressing BDNF in the postnatal brain of Mecp2 mutant mice slows down RTT disease progression, whereas removing BDNF in the same neurons accelerates RTT disease progression. These results implicate BDNF and other components of the BDNF signaling pathway as potential candidates for treating RTT patients. In addition to studying the role of BDNF in RTT pathogenesis, I have been searching for more MeCP2 target genes. Research along this line will help us fully understand how mutations in the Mecp2 gene cause RTT. Moreover, in collaboration with the laboratory of Dr. Sacha Nelson at the Brandeis University, I have identified a specific electrophysiological defect in the somatosensory cortex of the Mecp2 mutant mice. This assay will be a valuable tool to study RTT at the synaptic level.