Industry Experiences Shared by NIH Trainees
Brandon Brown shares his internship story ...
My internship for the summer of 2015 took place at the South San Francisco campus of Genentech. The lab where I did my research was part of the neuroscience department, building 15, located at 99 DNA Way, South San Francisco, CA 94080. Dr. Jesse Hanson, a bright young scientist, managed me during this internship and provided scientific and professional guidance when asked. Many times in lab, since our stations were set up near one another, I would pick his brain about company culture and organization. We also talked about career choices in addition to science. Jesse fostered an environment of discussion and was forthcoming when I asked his opinion of various things. I would characterize our brief relationship as strong and he was one of the reasons I had such a positive experience at Genentech.
Another person in the lab that was very important to my success in lab was another young researcher named Tzu-Ming Wang. Tzu-Ming was integral in showing me the techniques I would use in lab. He demonstrated expertise in the area of our particular research as well as taught me new, more efficient ways to analyze the massive amount of data I generated. He gave me a use for Matlab that I never considered before but will definitely use in the future. Another scientist whose lab Jesse is closely associated with is Dr. David Hackos. David is a well-known scientist in the ion channel field and usually provided ion channel expertise in lab meetings and in conversation. The Hanson and Hackos labs are doing great ion channel work, which makes me feel good about the direction of ion channel research at Genentech. It would be remiss of me not to mention another researcher in the Hackos lab who worked to deliver the necessary RNA to me to complete this project, Evera Wang.
The title of my project at Genentech was “Structural Determinants of NMDA Receptor Positive Allosteric Modulators (PAMs)”. NMDA receptors are ionotropic receptors gated by a combination of glycine and glutamate. They are expressed in the CNS and play critical roles in synaptic signaling and plasticity. Located postsynaptically, when activated, these calcium permeable channels lead to an inward current that carries significant calcium in to the cell that triggers downstream signaling. NMDAR hypofunction is thought to play a role in the pathophysiology of schizophrenia and NMDAR mutations have been identified in patients with epilepsy. Restoring impaired NMDAR function could also potentially treat the effects of Alzheimer’s Disease. Two NR1 and two NR2 subunits combine to form a tetrameric receptor composed of a transmembrane domain (TMD), and extracellular ligand-binding and amino terminal domains (LBD and ATD). Genentech put forth a major screening effort in order to identify compounds that can enhance NMDAR activation in the presence of glutamate and glycine. A library of 1.4 million compounds was screened and the hits were selected and further optimized in a series. For the sake of this work I focused on Series 1 and Series 2 compounds. The binding site for Series 2 compounds was previously determined but the binding site for Series 1 compounds is unknown. Understanding this was the objective of the project. In order to determine exactly where and how the compound was binding to the receptor I conducted an alanine scan of a region of interest. Using two electrode voltage clamp (TEVC) recordings of wildtype and mutant NMDARs expressed in Xenopus oocytes I assayed the function of each channel. While I am experienced in studying ion channels, I have never studied them in the context of oocytes. This is a higher throughput way in assaying channel function and a new technique I learned during my time at Genentech. Ultimately the data that I accumulated will be used to construct a model of the NMDA receptor, complete with the specific PAM docked at the binding site. I will also be included as an author on the published paper once it is written.
In addition to working on the project, I participated in several other activities as part of Genentech’s internship program. There were many activities that were valuable and amongst the most valuable were the seminar on confidentiality, speaker series (Tim Moore, Andy Chan, Cari DeLoa), GenenTank, poster event, LinkedIn information session and headshots, career panel, intern manager social, and the gRN networking social. Perhaps the most useful to me was the career panel. It was here where the interns were given practical advice, by HR personnel, on how to gain employment at Genentech and other biotech companies. I kept in touch with one of the HR representatives from the panel, Erin Krolikiewicz, and she put me in contact with an industry mentor, Joe Ware, that has already lead to some potential opportunities. In addition to the intern related activities there were some awesome seminar speakers who gave talks as well. Most speakers were leaders in their scientific fields and gave top notched talks. This created an atmosphere similar to that at UC Davis, where great visiting speakers would come speak almost on a weekly basis. Other perks included an excellent cafeteria, on site gym, free food at department seminars, sporting ticket giveaways, a great bus and shuttle system, department outings and great location by the bay. Probably the company’s biggest asset, though, is how nice everyone is. Genentech likely has the nicest, most helpful group of people I have been around. This very fact has made it one of the best summers I have had in my adult life.
Over all the internship had high educational value. I learned and participated in great science, and I had a great time while doing it. I wanted to do in internship at a big company and I wanted that company to be Genentech. I got both of my wishes and the experience was great. There was a period where I thought I would not make it since the commute (five hours total, waking up at 4am, and only getting five hours of sleep per day) was very difficult but all the things mentioned above kept me coming back. Now that the internship is over I’m a bit sad. However, I am optimistic that the connections I made during my three-plus months there will allow for a potential return. I am confident that I did a good job and I would welcome an opportunity to come back.