Presented by Thomas P. Sakmar
B.S., Stanford University
Studies of G Protein Coupled Receptor Stability and Dimerization Using Novel Fluorescence and Crosslinking Approaches
It is a privilege to present to you Adam Knepp.
Adam’s thesis research focused on how a particular class of cell surface receptors, called G protein coupled receptors (GPCRs), assemble in the cell membrane with other receptors to form a molecular nanomachine called a “signalosome.” He used a combination of computational and experimental approaches to model the disc membrane of the rod cell in the retina at the back of the eye. Adam showed that the light receptor called rhodopsin first forms pairs, or dimers, that then assemble into long rows. The rows then line up side by side forming a type of surface structure that resembles a toy slot car track. The slot between the dimer rows contains lipids from the bilayer.
Transducer proteins inside of the cell can hold on to the track and slide along the slot using their own lipid tails as they carry out a one-dimensional search for a rhodopsin that was activated by light — and only about 1 in 100 rhodopsins are active at any one time even in bright light. Imagine a protein sliding along a molecular slot car track on the membrane surface, and getting knocked off the track once it hits an active receptor — a protein “bump” in the road. Adam’s very cool model in part explains the fast physiological response to light in vision.
Adam also developed a very useful enabling technology to measure whether GPCRs are properly folded and how stable they are. Adam’s method attracted the attention of biotech and pharmaceutical companies, in part because his relatively low-tech, but clever method needed only about one ten-thousandth of the amount of material that they had been using in their own very expensive biophysical assays to measure basically the same thing.
One company currently using Adam’s technology was very surprised when they found out that Adam himself could produce the same amount of data in one week that it took three technicians one month to produce.
Adam’s innovative thesis work will continue to pay dividends to future lab members as his methods are more widely applied.
Adam received his B.S. in chemistry from Stanford University. He was a member of the so-called Facebook class. I first came across the term in a New York Times article about two years ago. In short, the Facebook class at Stanford was the first class that was given exclusive free access to the Facebook social media application that was being developed just up the road by Mark Zuckerberg after he moved west from Harvard.
When I asked Adam about the Facebook class, he said it was no big deal. Oh … but by the way, he has something like 800 Facebook friends! That is absolutely insane.
Adam is the type of person who never seems to have a bad day. He’s an enthusiastic problem solver and always seems to rise to the occasion, for example, as when I asked him to fly to Germany with one day’s notice to help with a major presentation at a very contentious meeting.
But Adam is one of the few people I know who has traveled more than I have in the past four years — with carefully planned adventure trips to Kilimanjaro, Machu Picchu and Southeast Asia. He also attended many Stanford Cardinals football games, including key bowl games during the Andrew Luck era.
Adam will start at McKinsey & Company this summer where his enthusiasm and skills will be put to very good use, I’m sure.