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Lorenz Mayr: Listen to the Data

Early on in his scientific training, SLAS member Lorenz Mayr, Ph.D., learned to let the data speak for itself. Be precise about interpretation, but don't over-analyze. Most importantly he learned that it is never OK to be "about right" – you have to be absolutely right before you submit work for publication.

 

Those lessons served him well, and Mayr is now vice president and global head of Reagents and Assay Development at AstraZeneca in Alderley Park, U.K. He has published more than 50 papers in peer-reviewed journals; has written a book, Label-free Technologies for Drug Discovery; and serves on several Editorial and Scientific Advisory Boards, including the SLAS Journal of Biomolecular Screening (JBS) where he is an associate editor. Mayr also is one of three guest editors for the 2015 JBS Special Issue, Screening by RNAi and Precise Genome Editing Technologies.

Building a Foundation for Great Science

"The biggest obstacles in my professional life were always on the technical side," he says. "Experiments didn't always work out as planned or the data were not as we expected them to be. That can cause problems, but it also makes you think about the bigger picture or the set-up of the experiment in more detail and often, not always, you will come up with a better plan."

His pragmatic state of mind and drive to overcome obstacles in his path helped him in his first steps to academic success when in 1985, he was admitted to the biochemistry program of the University of Tübingen in Germany.

"At that time it was the most competitive program in Germany and it was very hard to get admission," says Mayr.

He showed great promise and three years later, he was granted a fellowship by the German government to study at the University of Colorado at Boulder. This allowed him to develop on a personal level, he says, and "it opened my mind to other areas and cultures."

Next up for the young biochemist were doctoral studies at the University of Bayreuth with Franz-Xaver Schmid, Ph.D., which provided a strong foundation for Mayr's future work.

"Dr. Schmid taught me to ask precise questions to analyze the data," Mayr notes. "It was about generation of the knowledge and publication of that knowledge within the scientific community. You have to be the one who knows the most and makes the least mistakes. When you set up scientific ideas or models, describe what you have seen in your own way. You have to run proper controls and apply scientific rigor so that whatever you publish should be right.

"He was most interested in generating robust and scientifically profound data; publishing only the right data and not the most data," Mayr concludes. "It was about pure scientific knowledge, scientific understanding and scientific enlightenment."

Mayr earned his Ph.D. at the University of Bayreuth under Schmid and soon after traveled across the ocean once again, this time for a post-doctoral position at the Massachusetts Institute of Technology (MIT) Whitehead Institute for Biomedical Research in Cambridge, MA. It was at the Whitehead where he worked with his next significant mentor, Peter S. Kim, Ph.D. Kim is now with Stanford University following 10-plus years as the president at Merck Research Laboratories.

"Dr. Kim was quite interested in making a big impact in science," Mayr states. "He was one of the most ambitious and most influential young scientists, and I learned much from him at the Whitehead Institute. He went on to be the head of R&D at Merck with 16,000 people. He is an excellent science manager, and he piqued my interest in managing larger teams, groups and departments."

From both mentors, Mayr learned about "applying very high scientific standards in whatever we do – to do assay development in the best possible way, run proper controls and spend enough time to get it right. Excellence in execution is ultimately the key."

Putting Lessons Learned into Good Practice

Today, those early lessons are the cornerstone for each day's endeavor. They drive his research and guide his management as he sets rigid standards for excellence with his 120-member AstraZeneca Reagents and Assay Development teams in Alderley Park, U.K. (near Manchester) and Mölndal, Sweden (near Gothenburg).

"Our work covers all areas of biochemistry, molecular and cell biology, as well as some areas of physics and molecular medicine for all therapeutic areas within AstraZeneca," Mayr explains. His teams generate all the reagents and assays within their organization which are used for hit discovery, hit-to-lead, lead optimization and sometimes also for safety profiling. "This is extremely interesting work since every project has new challenges, needs new solutions and has different teams.

"I'm a very curious person, interested in finding new things that I haven't seen before," Mayr says. "I am always looking for new scientific professional areas to develop myself and the department. This curiosity brought me into science originally and then into science management in a pharmaceutical company to look for new medicines, new therapeutic areas, new targets and new technologies. This excites me over and over again."

Like his former mentor Kim, Mayr understands the importance of collaboration and working well with other people – both inside and outside of your organization.

"I have a rather large network across Europe and the U.S., due in part to chairing MipTec for about 10 years," he says. "I'm a very good networker and comfortable reaching out to people in different organizations – pharma, biotech, academia, technology companies."

He defines career success quite humbly as "if I stay excited, influence people, achieve objectives, learn something new and help people in their career progression, then I am having success."

SLAS Connections Fuel Success

The Society has been important to Mayr over the years, and his contributions have been many.

He served twice on the Society for Biomolecular Sciences Board of Directors and organized several workshops such as Proteases as Drug Targets – Challenges and Opportunities; Protein-Protein-Interactions; and the Grand Challenge of Modern Drug Discovery. For more than 10 years, he wrote reviews for JBS and the Journal of Laboratory Automation (JALA), earning JBS Reviewer Excellence Awards in 2007 and 2010.

"I have always very much enjoyed interacting with members of the Society and these connections have been very beneficial for me over the last years!" he says enthusiastically.

He advises all to embrace relationships with SLAS colleagues, not only on a professional level but also in a social sense. "When you face challenges, be aware that there is a large community out there. Reach out to your colleagues at work, but also to friends in your private and professional network. Most people are very happy to help. I think we can use the SLAS community much more for solving problems and to overcome challenges at work. It will be a pleasure for all involved."

Mayr practices this philosophy. Most recently, he had questions about confocal vs. non-confocal readouts in phenotypic drug discovery and reached out to his SLAS contacts at academic labs and in industry to ask 'what type of implementation' and 'what type of approach' would you recommend we use?

"Everyone was very helpful," he reports. "We saved a lot of time and money by just asking other people who have more experience than us."

Another example of relying upon colleagues with more experience revolved around phenotypic drug discovery in general. ?

"There is a lot of discussion about the field, so I reached out and asked questions of many about process, libraries, technologies and scientific concept," he says. "We don't need to invent everything within AstraZeneca; we need to just ask. Nine out of 10 times people are extremely helpful and very pleased to be asked."

As these examples show, he believes that SLAS is not only a networking opportunity once a year at the conference but is a community of experts to leverage throughout the year. "Simply pick up the phone and ask someone, 'what do you think?' I have no hesitation going East or West, North or South and have no preference for country," he continues. "I just look around and see who is knowledgeable and trustworthy."

Latest SLAS Project: Journal Special Issue Guest Editor

Mayr is truly excited about his role as guest editor for the JBS Special Issue, Screening by RNAi and Precise Genome Editing Technologies. His co-guest editors are Marc Bickle, Ph.D., of the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany; and Hakim Djaballah, Ph.D., of Memorial Sloan-Kettering Cancer Center in New York, NY. Manuscript proposals for their consideration are due Sept. 1 and invitations will be issued to prospective authors by Sept. 8.

"RNAi technology has been around for about 10 years now, and we've seen mixed success in the field using RNAi platforms – both siRNAi as well as shRNA," Mayr explains. "Using these technologies for identification and validation of targets, particularly genome wide screens for target identification, frankly has not delivered to expectation. Therefore, it is time to review the field.

"I think one of the biggest challenges in the pharma and biotech industry is the lack of good novel validated targets," he continues. "Whatever we can do to find better, novel and highly validated drug targets the more beneficial for industry and academic colleagues. The use of genome editing tools such as ZFN, TALENS and particularly the new CAS9/CRISPR hold huge promise for the generation of both genetically modified cell lines for screening, for target validation and ultimately for drug discovery.

"This is why we wanted to have a special issue of JBS and show that SLAS as a scientific organization plays a huge role in drug discovery with target discovery, modern biology and good biomedical understanding," Mayr explains. "There is a revival of RNA as a technology and also as a therapeutic, and we think inhibitory RNA methodology needs a proper re-evaluation by the experts in the field."

Making Time for Fun

Though managing teams in two countries keeps him on the clock constantly, Mayr does take some time for fun. His family and friends are happy that one of his hobbies is cooking, mostly Bavarian and Italian.

"A few items I cook are knödel (dumpling), sauerbraten, sausages," he states. "Perhaps these are not particularly healthy, but they are tasty! Schnitzel is not really Bavarian but it is another dish that I cook."

To balance his cooking interest, Mayr truly enjoys running – a pastime he can do wherever his travels take him. His usual run is about 10 kilometers.

"Running brings you away from your desk, and it is good for your cardiovascular health," he notes. "As long as I bring along my shoes, I can run anywhere. And I can run in winter and summer."

Mayr occasionally signs up for races as well. He recently finished in the top 25% at the Schweizer Firmenlauf (Swiss Company Run) in Basel, a beautiful route with city parks, wooden bridges and forest and meadow trails. More than 16,000 runners participated in the 5.6-6.5 kilometers run.

"I was very happy with my time in this race," Mayr notes. "I am getting better every year, and I need to continue to improve."

It is just one more way that Lorenz Mayr strives for excellence in all areas of his life.

August 18, 2014