Meet Alysha Joseph
Graduation Year: May 2016
Field of Study: Neurology and Neurotherapeutics
Autism spectrum disorders (ASDs) are a highly heritable group of neurodevelopmental disorders that affect as many as 1 in 68 children. Contributing genetic variants, including mutations in neuroligin-1 (NL1), neurexin-1 (NRXN1), and SHANK3, often play an important role in synapse development and function. NL1 is a postsynaptic cell-adhesion molecule that modulates excitatory synapse specification and function by stabilizing clusters of NMDA receptors at the synapse. In accord, our laboratory previously showed that NL1 knockout (NL1 KO) mice exhibit a reduction in synaptic NMDAR currents in the striatum, which correlate with increased repetitive grooming behavior. However, constitutive knockout of NL1 pre-conception does not allow determination of region-specificeffects vs. those derived from alterations in other brain regions. Therefore, we set out to induce a focal knockdown of this protein in striatum using RNA interference to determine the effect of this intervention on NL1 expression and the local expression profile of the NMDAR subunits NR2A and NR2B.
Since I was working in a neuroscience lab, one of the main challenges I faced was getting used to working with mice. However, I had great mentors to teach and guide me throughout my project and now I've pretty much become an expert at all sorts of techniques that involve mice, including IP injections, perfusion, and even stereotaxic intrastriatal injections. The experience has been invaluable and I believe that I will use the knowledge I gained for the rest of my life's work. The Green Fellowship helped me realize that science and medicine are inseparably entangled. You can't have one without the other!
Don't be afraid to ask questions! The more you know, the farther you'll go. Take full advantage of being at one of the leading research institutions in the nation: go attend some lectures and learn about the amazing world-class research that goes on at UTSW. If that's not motivation enough, keep in mind the fact that there's usually FREE food. Also, persistence is key. Your project may not go as expected and you may sometimes have conflicts with the people in your lab. Keep your head high, remember why you're there, and do the BEST that you can do with the resources you have. Good luck!