Creating Innovative Tools to Solve Complex Problems

With 15 issued US patents, 45 published patent applications and nearly 50 refereed publications, Michael Weiner, PhD, Vice President, Molecular Sciences at Abcam is an expert in molecular biology.

We recently spoke with Michael to learn more about the specific inspirations that ignited his interest in science. He tell us more about his particular research interests, the molecular biology methods that he has invented over the years, and his most recent work with Abcam.

Michael's talent for inventing isn't confined to the scientific field – as a keen artist and ceramicist Michael teaches novel ceramic techniques. He touches on the scientific inspiration he incorporates into his creative pieces. 

Laura Mason (LM): What particularly inspired you to pursue a career in science?

Michael Weiner (MW): For me it’s been the people I’ve been lucky enough to meet. I had great mentors in high school and college and worked in a research lab as a freshman Microbiology major at Penn State University. I’ve had forward momentum in my career and have learnt and grown from each opportunity, which has inspired me to continue my path in science. I’ve been especially fortunate to have had my entire career remain in research – without being sidetracked into other business aspects that might have also been as interesting.

LM: Could you tell us more about your current research interests and area of expertise?

MW: I’ve always been interested in molecular biology, even though my educational training focused on genetics and physical chemistry. I’m currently excited at seeing proteomics entering a phase where the right tools and methods will enable it to have the same impact that NextGen DNA sequencing – especially RNA sequencing – has had on the way we do ‘big science’ in biology. This means creating methods to increase the speed and accuracy of understanding the proteome to give researchers a complete picture of what’s going on in a cell. When I was at grad school, one lab looked at a single enzyme. Today, it’s changed to one lab looking at one human population and trying to answer complex problems, and we need to provide researchers with the tools that will help them do this more easily.

Abcam’s FirePlex^® system is one way the Company is approaching this ‘big picture view’. The technology allows the simultaneous multiplexing of up to 75 proteins or 65 miRNAs from low sample volumes and crude biofluid. We’ve recently expanded this technology into FirePlex^®-HT, which is a high-throughput version of our FirePlex immunoassay. FirePlex-HT is aimed at pharma and clinical researchers and offers 384-well plate format and quantification of up to ten analytes per well. And there are still plenty of other things we’re innovating that will participate in this future, too!

LM: You have invented many molecular biology methods. Could you tell us more about some of these methods?

MW: The ‘80s and ‘90s were a great time for inventing at small molecular biology tools companies as the tools we know today weren’t available at the time. To begin with, I’d look to see which protocols researchers used and then try to come up with clever ways to increase their efficiencies – mainly by selling reagents and kits that were quality controlled to work together. The intent was to allow our colleagues to solve their scientific questions without worrying about the means they used to get there. So, we invented PCR cloning and expression kits, QuikChange mutagenesis kits, cDNA library kits, etc. These kits made certain methods of molecular biology a lot easier to perform and enabled researchers to get answers faster.

In the ‘00s, I worked on more macro-projects, like high-throughput SNP genotyping, at a large Pharma company and leveraged this large-project experience to rejoin a small biotech and switch my focus toward instrumentation applications. Specifically, de novo DNA sequencing. Trying to address the astounding challenge (at the time), “How would you sequence a human genome in a day for less than $1,000?”

Now, at Abcam, I can innovate at both the large and small levels. For example, one or two team members developed the pMINERVA scFv to IgG conversion vector system. This is more accurate technology because you’re doing everything inside of the cell. It reduces the time to make recombinant antibodies as it converts fragments into complete antibodies. And more recently at the larger end, we have yet-to-be-disclosed projects that take a whole team of nearly 20 people to develop.

LM: How does it feel to have many of these technologies become commercially available for others to use?

MW: That’s my favorite part. I’ve been mostly focused on providing tools to researchers, so they can solve what I feel are the real scientific questions. Like “How does this work?”, “How did we (as humans) get here?”, and “How do we cure this?” Knowing that something I’ve seen develop from just a thought on the drive home from work, to (eventually) the commercial market is the reward. Researchers pay precious grant monies for the things we make. Both in the past and now at Abcam. So, it must be reproducible, and it must do what it’s supposed to do. It’s a unique feeling and something I’ve been privileged to have several times in my career: to make something that has value and fills an unmet need.

LM: Could you tell us more about your work with Abcam on the development of recombinant antibody technologies?

MW: My focus is to develop technologies that create reproducible recombinant antibodies, faster. Because recombinant antibodies are made from a unique set of genes, enabling a more controlled and reliable method of antibody production, they offer improved consistency and are highly reproducible. The phage display technology we developed also means we can make antibodies within 8–10 weeks, particularly for trickier targets.

Currently, my research is mostly focused on proteome analysis. I’m very interested in a future where we can do ProtSeq as easily as RNASeq can be performed today. My ultimate goal would be to have antibodies to the complete proteome, including post-translational modifications at or nearly at amino acid resolution. So, in the future, you don’t tell us which protein you want to target, but which amino acid on that protein do you want to take a look at. This will enable researchers to ask much more specific questions than they can do with the tools available today.

LM: What have some of your most rewarding achievements been so far?

MW: As I tell the people I work with all the time, it’s never about the projects, it’s always about the people. Seeing people succeed at achieving something you already believe will work is the greatest reward. As a technology, I’d have to say QuikChange mutagenesis. Used in protein engineering, it changes amino acids in a protein so you can study the effect of amino acids in diseases.

It’s been cited about 50,000 times in the literature so it’s very reproducible and extremely useful. As an instrument, I’d have to say developing the 454 instrument which was the first genome sequencing platform on the market. It was extremely challenging to develop the instrument and method simultaneously. We did the impossible – in just two years bringing that technology to market.

But it’s always the latest projects which reflect some of the best science I’ve ever done. In the last few years at Abcam, we’ve developed some amazing antibody technologies that are fast to develop and highly reproducible. Some of which, like pMINERVA, AXM Mutagenesis, and PDC libraries, have been published and are being used daily in our internal antibody discovery pipeline. And some other projects, which I’m sure we’ll discuss soon at some meeting or in a publication, will astonish people even more and give them an idea of the high level and quality of innovation taking place at Abcam.

LM: I notice that as well as your interest in science you are a keen artist and ceramicist, could you tell us more about this? Do you incorporate a lot of scientific inspiration into your creative pieces – and vice versa?

MW: I’m almost ashamed to admit that I originally took all my electives as an undergrad in ceramics mainly because the art center was located next to my dorm building. And it gets really cold in State College, PA in the winter. But through the years, I’ve kept up my ceramic skills and use it as a creative outlet. I’ve specialized in transferring images onto clay and have even taught workshops on techniques I’ve invented. I’m inspired by my work in the lab – lately I have been working on recycling plastic disposables from the lab for art projects and I’ve recently approached our building committee about doing a multimedia piece for the Abcam headquarters being completed in Cambridge, UK.

Michael Weiner, PhD, was speaking to Laura Elizabeth Mason, Science Writer for Technology Networks.