Perspective On: A Drug Discovery Lab

The privilege of conducting research dedicated to finding cures for human diseases is one reason Paul Diaz starts his workday with enthusiasm. “The life of a scientist can be stressful, but in what other profession does it seem like someone is is paying you to indulge in a guilty pleasure?”

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The privilege of conducting research dedicated to finding cures for human diseases is one reason Paul Diaz starts his workday with enthusiasm.

“The life of a scientist can be stressful, but in what other profession does it seem like someone is paying you to indulge in a guilty pleasure?” says Diaz, director of laboratory operations at the laboratories of Dr. John C. Reed, Sanford-Burnham Medical Research Institute, in La Jolla, California.

“I wake up and can hardly wait to see the latest results and make the next discovery.”

Diaz manages a drug discovery lab whose primary focus is to find and characterize potential molecular modulators—chemical matter such as small molecules, natural products, and biologicals, among others— for the purpose of developing therapeutics. Specifically, his lab focuses on cancer biology and inflammation.

“Within those broad categories, we’re focused on the study of cell survival mechanisms involving the Bcl-2 family interactome, its functions and relationships to cancer; autophagy, the mechanism by which cancer cells may survive nutrient deprivation; ER stress, the property of cells to respond adaptively to excess synthetic pressure or unfolded/ misfolded protein in the endoplasmic reticulum (ER) versus cellular alarm responses that can lead to cell death; protease signaling networks; and, finally, the molecular mechanisms of inflammation,” he says.

“We find all these areas can tie in at various levels, and thus we find new functions for the various apparatus within the cell, spurring on new questions and exciting discoveries.”

Lab structure

The laboratories of Dr. Reed consist of four 1,250-square-foot rooms and two tissue culture rooms that are jointly about 900 square feet. Diaz manages this roughly 5,900-squarefoot space in which 30 scientists and two administrative assistants work.

“The institute has many other labs, but the main campuses are here in La Jolla and in Lake Nona, Florida,” Diaz says. “The La Jolla campus is centered on cancer, infectious disease, and inflammation, while the Lake Nona campus is centered [on] diabetes and obesity.”

As lab director, Diaz is in overall operational control of the lab and of the drug discovery projects. He is in charge of the day-to-day operations and reports directly to the principal investigator (PI) of the laboratory, Dr. Reed, who is also the CEO of Sanford-Burnham Medical Research Institute.

In Diaz’s lab, team members, called research associate professors and staff scientists, manage nonoperational aspects of the basic research as well as mentor and support the post docs.

“The scientists in our lab are all biologists from various disciplines including immunology, oncology, inflammation, cell biology, biochemistry, physiology, and pathology,” he says. “Occasionally, we will have a chemist join our ranks, but generally they work with other laboratories here that specialize in medicinal chemistry.”

Nearly all the lab scientists hold PhDs and are either permanent staff or post-doctoral trainees.

Diaz studied biochemistry, biophysics, and molecular and cell biology and holds a PhD from University of California, Berkeley. After finishing his education, he started working in industry, where he gained a true appreciation for the spectrum of drug discovery and translational medicine tools and technologies that can greatly facilitate scientific discovery.

“Most notably, I learned quite a bit about robotics and instrumentation from very talented engineers,” he explains.

Diaz was then recruited to build and operate a high-throughput screening and compound control facility for a well-known pharmaceutical company. Using the skills he gained in industry—as a project manager, a scientist, and an automation biologist—Diaz worked with architects to design the lab and then purchased the necessary equipment and established the operating budget. Additionally, Diaz handpicked his staff and created a successful development plan for each member. He was later retained to direct the newly established operational excellence office responsible for applying Lean Six Sigma.

His experience in drug discovery and operations makes him uniquely suited to manage a large laboratory involved in basic and translational research. So when an opportunity arose at Sanford-Burnham, Diaz was the right match.

“In this capacity, I run operations, hire staff, run drug discovery projects, and mentor junior researchers,” Diaz says.

Maintenance and inventory

To ensure that the instruments are in operating condition at all times, Diaz has delegated maintenance of the lab’s instruments to the staff and post-doctoral trainees. The operators inspect all instruments weekly and upon each use.

“The weekly inspections include calibration tests, cleanup, and parts replacement when necessary,” he says. “Each staff member is given an area of responsibility and will typically fix instrument problems or report them to me."

When an instrument goes down, a staff member logs the problem on a shared database. Then an email notification is sent to other lab members, so they can plan their procedures accordingly.

“Actions taken to repair the instrument and bring it back on line are tracked in the same log so all can see the progress of repairs and know the disposition of all instrumentation and equipment in the lab,” Diaz explains.

Diaz, who manages the lab’s inventory, uses the Kanban system— an inventory and scheduling system. The system keeps track of the thousands of SKUs (stock keeping units) required to support a lab of such size.

The staff keeps all supplies and reagents in designated storage areas. Diaz performs large-case inventory twice a week and keeps a certain number of cases of each supply on hand.

“Open cases of these items are considered as ‘in use’ and do not count toward calculating orders,” he says. “For the Kanban system to work on the multitude of smaller SKUs, ordering information must be written on the case or box.”

When an item is exhausted, the last person who used the item delivers the box to any staff member. That member will then place an order for the item using an electronic marketplace called SciQuest.

“The orders are routed to me; I approve them and run analyses on demands for certain reagents to help me project and manage my sales and Perspective On: A Drug Discovery Lab operations,” Diaz says. “In addition, and to limit cost incurred by mishandling or overconsumption, we routinely aliquot reagents into small-use portions and provide them to lab members in this format.”

Hiring

Diaz believes that hiring the right personnel is a critical aspect of running a successful laboratory, especially for a drug-discovery or high-throughput screening (HTS) lab.

“It’s important to have people with diverse backgrounds working in the lab,” he says. “Having people with backgrounds varying from chemical engineering and computer science to biochemistry and cell biology will help to creatively and effectively solve problems due to the various perspectives applied by each person.”

To ensure the broad range of skill sets within his team, Diaz and his boss take care of the hiring themselves. Diaz is in charge of hiring technicians, while his boss hires post-doctoral candidates and staff scientists.

“Hiring is conducted by advertising positions and then gathering resumes via our website, and by direct recommendation from other researchers,” he explains. “Technician candidates are vetted by their skill sets and experience and then invited for an interview.”

After an interview, Diaz and his boss check references and, if the person is a good fit for the lab, they make them an offer.

“As to post-docs, generally a candidate will send us a letter outlining their interest and we evaluate the fit,” Diaz says. “We also ask for letters of recommendation from their referees. If we think we can accommodate them, we invite them for an interview and to present a seminar on their current work.”

“If we feel they can conduct the types of projects that interest us, then we may make them an offer within a few days.”

Challenges

Running a successful lab with a variety of personalities is not always easy. And for Diaz, the biggest challenge is ensuring all those personalities mesh with each other and with the overall goals of the lab.

“They are the key resource of the lab and the most likely wild card in play,” he says. “Everyone has their own agenda and things that motivate or discourage them, so I need to be aware of these personality differences to ensure that disparate and sometime antithetical philosophies embodied in certain lab members can productively and peacefully coexist.”

But it’s his staff ’s commitment to the bigger picture that helps Diaz overcome this challenge.

“I firmly believe that everyone comes to work with the idea of doing a great job, so I try to build on that presumption by keeping the work challenging, involving people in decision processes related to the work they do, and listening carefully for their suggestions on how to do it better in all respects,” Diaz says.

For that reason, communication becomes an extraordinary tool in Diaz’s management repertoire. To him, it’s the single most important tool a manager could utilize in maximizing efficiency and reducing waste.

“Ensuring that team members have timely decision-level information and work plans is tantamount to actually doing the experiments,” he says. “An incredible amount of time, energy, and money is wasted by poor communication and poor planning.”

Another element that keeps things interesting, while posing its own kind of demands, is the lack of a daily routine.

“You have to be able to react quickly and come up with adequate solutions to the myriad of problems that spring up every day,” Diaz says. “However, there are certain elements of the day that must be managed and addressed often. These involve project planning and control, supply chain issues, analysis, and reporting of results.”

Diaz overcomes this challenge by allowing his staff to escalate any problems to him, so they can focus on the job they were hired to do.

“I guess you could say that the entropy in the system is absorbed by me so the lab members can get their work done in an orderly and efficient manner,” he says.

However, the honor of conducting research that benefits others in the areas of science and health makes all these challenges seem insignificant.

“Our lab has been one of the leading labs in the study of apoptosis and its relevance to cancer biology and inflammation,” Diaz says. “We have made significant contributions to the understanding of these cellular mechanisms from a basic research perspective.”

Management tips

Diaz believes that every manager can use a small checklist to ensure that a drug discovery lab runs without a hitch. A reliable staff is a must, he explains, and while hiring the right personnel is important, it’s also critical to give each person the right skill set.

“Encourage your people to cross-train and broaden their skill sets to avoid developing the culture of ‘the genius with a thousand helpers,’” Diaz says. “Cross-training will also allow for better problem-solving because team members become more invested in areas that are not strictly within their areas of expertise, [and] will compensate for adverse circumstances or sudden changes in workload, personnel and resource availability.”

Once a manager has put together a dream team, it’s important to champion the laboratory.

“Put a positive message out to other departments and labs about the desire to collaborate on projects and the technical virtuosity of your people,” Diaz explains. “Promoting the welfare of your most critical asset—the people who support your leadership—will pay off in advancing your career and theirs.”

Next, it’s important to make the lab’s technology and resources available to other labs.

Make the access procedure simple and clear so that the lab staff can accept additional work in an orderly fashion Perspective On: A Drug Discovery Lab and to avoid having them pulled into too many directions at once, Diaz says.

“Integrating your lab into the larger fabric of your organization will put you in a position to take advantage of research and business opportunities you normally wouldn’t notice, and will help you make a greater contribution to the success of the organization as a whole, for which you and your people will gain recognition,” he explains.

It’s also important to simplify. Diaz achieves this by developing and using flow charts and quick start guides to complement standard operating procedures (SOPs).

“These tools can help give people who use your systems, or access your people and technology, an overview of your idea of orderly and efficient work,” he says. “They can also serve to remind even experienced users of the key steps in procedures, especially in cases when the procedures may be run infrequently.”

Visual indicators—whether it be a poster or a chart—could also show important touchstones or procedures in the lab.

“Visual controls can make problems, anomalies, or deviations from expectations visible and obvious to everyone so that appropriate action can be taken,” Diaz says.

Diaz’s last and perhaps most important tip is to engender a convivial atmosphere.

He achieves this by encouraging collaboration, giving sincere praise, recognizing that people don’t fail as much as the process does, giving onthe- spot awards of a free lunch for unexpected contributions, catering weekly brainstorming sessions, and throwing the occasional party.

“In the future we will establish monthly birthday parties where folks can have pizza or other fare while signing off in each others’ notebooks,” he says.

Top Instruments

  • Plate readers of various sorts, including the PerkinElmer Envision and the Molecular Devices Analyst
  • GE Akta FPLCs for purifying proteins
  • Robotic liquid handlers, such as the Biomek 2000, and Biomek FX workstations

Sara Goudarzi is a freelance writer based in New York City. Her website is www.saragoudarzi.com.

Published In

Go, Go Gadgets Magazine Issue Cover
Go, Go Gadgets

Published: July 5, 2011

Cover Story

Go, Go Gadgets

Continuous advances in mobile technology have been changing the way the modern world works. Make last-minute changes to a presentation on your way to a meeting, send reports back to the office while you’re at a conference or trade show, or even input data from an experiment into the LIMS directly at the bench.