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Science AMA Series: I’m Michael F. Wells, a Postdoctoral Fellow at the Broad Institute and Harvard University. I hack into the minds of genetically-engineered mice to better understand psychiatric dise
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Hi Reddit, My name is Michael F. Wells and I am originally from Columbus, OH. Ever since I read the book “The Value of Believing in Yourself: The Story of Louis Pasteur” when I was five-years old, I wanted to be a scientist who studied human disease. I recently completed my PhD at Duke University and am now conducting research at the Broad Institute and Harvard University in Cambridge, MA. My work focuses on creating models of psychiatric disease to unravel the mysteries encasing these complicated and debilitating disorders so that one day we may be able to produce safe and effective treatments. I spent the past 6 years in the laboratory of Dr. Guoping Feng at the Massachusetts Institute of Technology where I was involved in projects focusing on animal models of obsessive-compulsive disorder (OCD), autism spectrum disorder (ASD), schizophrenia (SCZ), and attention-deficit/hyperactivity disorder (ADHD). I now work in the laboratory of Dr. Kevin Eggan where I am using human stem cell-derived brain cells to study some of these same diseases. This past week, my work focusing on a new mouse model of ADHD was published in Nature (http://www.nature.com/nature/journal/vaop/ncurrent/full/nature17427.html). In this study, my amazing team from the Feng lab and the Michael Halassa lab (NYU) removed a gene known as Ptchd1 from the mouse genome (known as the Ptchd1 knockout mouse). We picked this gene because it has been found to be mutated in approximately 1% of patients with ASD and intellectual disability (ID). These mice displayed several abnormal behaviors including cognitive deficits, grip weakness, disrupted sleep, hyperactivity, and attention deficit. Importantly, we found that Ptchd1 is expressed in a part of the brain known as the thalamic reticular nucleus (TRN), which acts as an “information filter” in the brain. The results of our investigation suggest that this filter is allowing too much information to pass through to other brain regions in this mouse. Importantly, we were able to show that these TRN defects were contributing to the hyperactivity and attention-deficit behaviors, both of which are hallmarks of ADHD. Finally, we successfully fixed these ADHD-like behaviors in mice using a drug known as 1-EBIO, which targets an ion channel that we found to be dysfunctional in Ptchd1 knockout mouse TRN cells. It is important to note that 1-EBIO is not meant for use in humans, so much more work needs to be done before we can translate these findings to a safe and effective treatment for humans. Are mice valid models for human conditions? How do you assess these human-like behaviors in mice? What is the future of disease modeling? I will start answering these questions and more around 1pm (10 am PST, 6 pm UTC) and will stick around until you get tired of listening to me. Edit: OK I’m starting early because I am the captain now. Let’s do this. Edit #2 (1:47pm): I had some technical issues. They are resolved now so I am back. Edit #3 (2:44pm): I am staying until you kick me out. If you have to leave, however, and want to continue the discussion, you can follow me on Twitter @mfwells5 Also, my collaborators and I have set up a Gmail account to answer Ptchd1/TRN questions: [email protected] Final Edit (6:50pm): Thanks everyone for your amazing questions. I answered as many as I could before my stem cells started crying for their daily feeding. Feel free to reach out to me if you have any additional questions. It was fun–see ya!