AT A GLANCE
NAME: Jay Boniface
POSITION: Senior Director, Protein Science and Proteomics, Myriad Proteomics
PRIOR EXPERIENCE: Started proteomics group at Eos Biotechnology
What is your educational background?
I got a bachelor’s degree in biochemistry at the University of Massachusetts at Amherst, and my PhD was also in biochemistry from Albany Medical College in Albany, NY. Then I did a postdoc at Stanford in Mark Davis’ lab in immunology, working on T cell activation and T cell receptor biochemistry and biophysics.
Why did you choose to study biochemistry in the first place?
I fell into it. I was never the type of person who knew what he wanted to do from day one. Originally my plans were to go into engineering, but then when I was taking some initial courses that were more mathematically intensive as an undergraduate, I started to realize I was more skilled in biology. I remembered that as a kid I had more fun looking for salamanders in streams than I did crunching numbers. I started taking biology courses and that led to biochemistry, and then I realized that I was comfortable enough with chemistry to bridge those two and just focus on biochemistry.
How did you get involved in proteomics?
When I got through at UMass., I realized I wanted more than what I could get in science with a four-year degree, and I was interested at that time in how cells communicate with each other, and in particular how hormones act to allow cells at a great distance from each other to talk. I knew that the department of biochemistry at Albany Medical College, which was close by to where I grew up, was very strong in glycoprotein biochemistry, so I went there to do my PhD basically to learn about glycoprotein hormones.
While I was there, I made an observation with regard to a unique activity that the hormones had, which was the first report of these hormones having an oxidoreductase-type activity — disulfide isomerase-type activity. I was then looking for something new, and I realized that one system where cell-cell communication was very important, and where there was a need for people with a biochemistry background, was in immunology.
I started looking for a postdoc in immunology, having never taken a class in immunology—I still haven’t. I contacted Mark Davis at Stanford, interviewed with him, and he accepted me. That was in 1990. Mark’s claim to fame was that he cloned the T cell receptor genes. At that time, in 1990, he had just finished making soluble expression versions of T cell receptors and their corresponding ligand, which is an MHC molecule, a histocompatibility molecule, so he needed protein people to start working on how these two proteins interact. I was the first protein biochemist to come into the lab and to start to think about how to purify these proteins, and how to study them.
The other thing that’s relevant is if you go back to my graduate work, the glycoprotein lab that I worked in was really the foundation of what is now proteomics. That laboratory was what is often referred to as a ‘grind and bind’ laboratory, where you take an animal tissue, grind it up and see what binds to it. You label the protein with radioactive labels, and see what it will bind to in a particular tissue, or a particular cell-type within the tissue, or a particular membrane fraction that came from the tissue that you basically homogenized.
At Stanford originally I had the hope of turning myself into a molecular biologist, [but because of what] my skills and interests are, what I ended up doing was much more protein biochemistry and much more protein biophysics. We bought our first Biacore machine in 1991 or 1992, and it was my responsibility to begin to run that machine and to study the kinetic rate constants for T cell receptor — MHC interactions. While I was there I also did experiments in biophysics, studying the conformational changes in MHC by fluorescence energy transfer. That was done in collaboration with Lupert Stryer’s lab. I also did thermodynamic studies, and cytosensor experiments.
I think what comes out of that is that I was a protein biochemist who became a technophile, and at that point I started to look at what fields were appropriate for someone who had skills in protein purification and protein biochemistry, and who enjoyed new-generation technologies that would help answer questions in this field. It was obvious that this new and emerging field of proteomics was a good place to go.
In 1998 I joined Eos Biotechnology in South San Francisco to build and then run a proteomics group there.
Why were they interested in doing proteomics?
They are a DNA array genomics company that wanted a proteomics group built that would complement transcript profiling. I was the 25th person hired, the company is now in the 90s, and when I left there were about 75 people. I did go straight from a postdoc into that, but it was an eight-year postdoc. I was at Stanford from 1990 to 1998.
In February [of 2001] I joined Myriad Genetics in anticipation of Myriad Proteomics.
What was it like over at Eos? Was the group you built over there successful?
I was hired by friends and I’m still really close with everyone there, and it was a good parting. The reason why I left was that after three years at Eos, the opportunities at Myriad were more consistent with my interests in proteomics.
While at Eos, while I was developing the proteomics platform, [I became involved in] 2D gel mass spec-based protein discovery. The other technology that I was working on that was relevant to proteomics is surface chemistries for protein and antibody arrays, and high-density protein spotting on such surfaces.
When I joined Myriad that was to build the foundations of [the platform for using] mass spectrometry for profiling multiprotein complexes. I joined Myriad Genetics to follow opportunities in proteomics, and I was charged with building this mass spectrometry platform for profiling multiprotein complexes. That technology then became part of the spinoff, Myriad Proteomics.
You had had experience with mass spectrometry?
At Eos we were completely MALDI-based in the proteomics platform that I built, and I had limited mass spectrometry experience while at Stanford.
Were there others starting at Myriad on the proteomics spinoff when you joined?
The spinoff was initially built on technology development [that was done by] Myriad Genetics employees. I was hired as a Myriad Genetics employee, in anticipation that if the Myriad Proteomics deal happened I would join the startup. I think I was one of the first people to officially sign on with Myriad Proteomics. The other key point is that at the end of January of this year, after building Myriad Proteomics to about 50 people within Myriad Genetics, we relocated to our own 36,000-square-foot building, and are continuing our hiring process. My title is senior director of protein science and proteomics and I report to the CSO, Sudhir Sahasrabudhe.
What kind of work were you doing while still a Myriad Genetics employee?
It was technology development in molecular biology, protein expression, vector design, protein purification and pulldowns, and mass spectrometry itself.
How similar is Myriad’s approach to that of Cellzome and MDS Proteomics?
What we’ve built is very similar to what MDS and Cellzome do. The big difference is that we combine [the protein complex pulldown] platform with a very high-throughput yeast two-hybrid process, which is not part of my reporting structure.
Are you involved in the yeast two-hybrid work at all?
I’m involved in it, but I’m not responsible for that. I’m involved in it as far as the data that’s generated there triggers events that happen on the mass spec side, and I’m involved in hiring and in meetings at the director level with that group. We’re all housed in the same building. The yeast two-hybrid side of Myriad Proteomics is essentially a technology transfer from Myriad Genetics’ ProNet platform, headed by Paul Bartel. Bartel has stayed at Myriad Genetics.
Is this the first time someone has combined pull-down with yeast two-hybrid techniques?
I think on a large scale, yes. I can’t name a paper but I guarantee if we look we can find PubMed papers [in which people] did a yeast two-hybrid experiment and then confirmed interactions by mass spec. My guess is that the data sets would overlap but not be identical, but I can’t put my finger on [one paper] right now.
Are there other things beyond what you’re doing now that you’d want to do professionally?
I think that I’m interested enough in startup companies and in upper management and business issues to continue to try to grow within the ranks of the biotech industry in the short term. I haven’t given up on the fact that I like teaching, and I miss teaching, and that I might consider returning to academics. Perhaps in a semi-retirement mode [I’d like to] do some teaching in a small liberal arts college environment, where I would ride my bike to class every day.