Perspective On: A Cancer Research Lab

For lab manager Mark Lloyd, finding the motivation to come to work every day isn’t difficult. All it takes is an extra-long walk—a routine that started when he was a master’s student working at a shared resource facility at Georgetown University.

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Helping patients is the fuel that drives this lab

“They [university staff] had asked me—when I came in through the campus—to walk through the hospital and the cancer center so that I could have exposure to patients. That way, as I got to the lab, I would have a very poignant reminder of why we were doing this kind of work,” he explains.

Now manager of the Analytic Microscopy Core (AMC) facility at the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida, Lloyd continues to “park in the most inconvenient parking lot possible” so that he has “the opportunity to walk through the clinical areas on a daily basis, twice a day minimum” to remind himself why his work matters. “Because I feel this work is so very important, I encourage my staff to do the same,” he says.

That work involves imaging anything that requires a microscope to see as well as analyzing those images.

The Analytic Microscopy Lab team, right to left: Tingan Chen, MD, PhD; Mark Lloyd, MS; Marilyn Bui, MD, PhD; and Joseph Johnson, MS. Not pictured: Agnieszka Kasprzak, MS.“It used to be that a picture was worth a thousand words and taking that picture would be substantial for publication and so on, but now a number is worth a thousand pictures,” says Lloyd, who has worked in cancer research for 13 years, ten of those at Moffitt. “We are not only responsible for the image acquisition, but we also do very extensive and customized image analysis to be able to provide Moffitt and other researchers the opportunity to interrogate and understand their biological processes at the microscopy level of resolution.”

The AMC is broken into three segments: cell imaging and analysis, digital pathology— which deals with tissues imaging and analysis—and the vivarium area, which covers live imaging of animals. Lloyd reports to a scientific director, and the lab also has three full-time research specialists I, II, and III.

“We also have a number of interns who come and go throughout our calendar year,” Lloyd adds.

Those staff members have a range of education levels, including MD, PhD, and master’s degrees—education that is key to working with those using the AMC.

“Level of education is very important for scientists in a shared resource setting to be able to have a conversation with principal investigators to assist them in their experimental design and in suggesting or discussing the kinds of image analysis that would best meet that investigator’s needs,” he explains.

However, he adds employees don’t necessarily need to be experts in the investigators’ areas of research, and the training they receive when they start at the facility is just as crucial.

“We need to be trained in what is available in terms of the technology to be able to answer the questions that they [principal investigators (PIs)] bring to us,” he says. “In that regard, I find in many cases the training that these employees receive is more important to them than the education that they come with. I would prefer to have a ‘blank slate’ than necessarily go to the market with a fine-tooth comb trying to find the perfect candidate.”

Joseph Johnson uses a confocal microscope to image the mitochondria (red) and microtubules (green) in cancer cells.Dr. Tingan Chen uses a multiphoton excitation microscope to image tumors in animals under anesthesia.

 

 

 

 

 

 

 

 

That training involves a course module designed especially for the AMC, which gives new staff exposure to all areas of the lab and allows them to both meet the facility’s needs and pursue the area of microscopy they enjoy most. In their first year, employees are sent to at least two different external training programs, which they get to choose with management’s help.

“Those programs vary a great deal depending upon which areas of interest those individuals have identified … and where they feel comfortable and where we really need them,” Lloyd says. Programs can range from intense weeklong training sessions to weekend or two-day overnight programs focused on a specific technique.

For Lloyd himself, a business background is also important to his job.

“My training is in both tumor biology and optical microscopy, but I also have an MBA to help me with the kinds of financial and management decisions that need to be made for the laboratory,” he says.

Workload and roles

The knowledge of Lloyd and his staff stands them in good stead, as they can get as many as 20 projects a day, though the average is usually half that.

“We are a volume-driven facility, and so we receive about ten different projects a day from individuals who are coming in for image acquisition, coming in with their samples to take some pictures,” he says.

The AMC staff also act as teachers, training the researchers who utilize the facility how to use the instrumentation to a point where they are comfortable and can come in 24/7 to work unassisted on projects that require a lot of time.

Agnieszka Kasprzak evaluates a time-lapse experiment in a live-cell incubation chamber.As lab director/manager, Lloyd is responsible for many tasks, reporting to a scientific director and advisory council to ensure that the techniques and expertise the AMC offers are those required by the Moffitt faculty. He looks after employee satisfaction, designation of longer projects, personnel management, and experimental design. And he’s taken on the added task of obtaining and managing his own government-funded grant projects for the development of new tools to be used within the AMC.

“I try to work as a kind of hybrid of a PI lab and a core research/shared facility,” he says. “I’ve been here a decade, and I really enjoy what I do as a staff scientist in the core facility, which is really the right role for me. I really enjoy being in a [microscopy] core facility.”

He adds that, in particular, working with the microscope to meet researchers’ needs and designing experiments is a lot of fun for him.

“I enjoy being a scientist,” Lloyd says. “I like being able to think critically about the kinds of problems that arise. I think even more satisfying for me, personally, is the ability to design that experiment. I will bring the whole team together for something that’s really challenging and we’ll brainstorm through it and begin to map it out.”

An average day in the lab always begins with a team discussion, when they figure out what will be done that day and go over anything important from the previous day or week that hasn’t been addressed yet. The AMC’s online scheduling system notifies the staff of their roles and responsibilities for the day, which are dictated by the investigators making the requests. Throughout the day, staff perform the listed functions to ensure projects are completed, reported on, and communicated back to the investigators.

“We kick off at 9 o’clock all knowing, basically, what our schedule is going to be for the day,” Lloyd says. “By the time we leave at 5:30, we have the next day’s schedule already available so we can mentally prepare for the tasks that will be at hand the next day.”

To motivate staff to power through those days, the AMC has a lot of small rewards, based on the personal preferences of the staff member being rewarded, which are put in writing during year-end evaluations.

“I motivate my staff in the ways that are best for them individually,” Lloyd explains. “As you can imagine, microscopists who spend a lot of their time in a dark room may have different kinds of preferences for how they are acknowledged and so on.”

Those rewards can be anything from going out to lunch together to fun, inside-joke type gifts. “These types of team-building exercises, when appropriate, can be very impactful for the individual, and so that’s the way we like to motivate each other.”

Lloyd himself spends a lot of time in meetings but prefers the lab, despite the challenges.

“My greatest challenge is being able to satisfy the myriad of different kinds of ideas that come through the lab,” he explains. “An investigator’s imagination is the limit of what could be requested of us, and this is a challenge intellectually, but it’s probably the most fun part of this job.”

Technology and the training and research it involves, because technology is always changing, are a big part of meeting that challenge, Lloyd says.

“We try not to let an investigator come to us with some kind of novel technology that we don’t already have some understanding of—how it works and what it does,” he says. “This gives us an opportunity to think as scientists about how we can solve these kinds of problems. Preparation is what leads to success.”

The AMC uses a variety of microscope and image analysis technologies, both from big brands and smaller vendors, in order to stay flexible for the variety of requests they receive from PIs. A LIMS also helps keep things organized.

“Each one of these companies has its strengths and weaknesses, and we very much understand what each of those is, so we like to not pigeonhole ourselves into one specific brand or model but to be as versatile as possible with each of these systems,” Lloyd says.

Super-resolution has been one major development in microscopy.

Mark Lloyd uses a multiphoton microscope to investigate tumor growth in an animal under anesthesia.“In the past few years, techniques have emerged that defeat the laws of physics computationally and enable what is called in the field ‘superresolution,’ which just innately changes how well we can see really small things,” Lloyd explains. “This is very exciting for us and for the investigators at Moffitt [who] require that kind of technique.”

More broadly, there’s been a big increase in lab automation in the cancer research field, in making instruments easier to use, and in the need for objective quantification. Lloyd says these changes mean the AMC is focusing more on image analysis than ever before. Whereas it once took up around ten percent of their time, image analysis now consumes about 60 percent of it.

“It’s been very exciting to be able to move with the technologies and be able to take advantage of them, because they certainly are beneficial for the investigators and the kinds of questions that can be asked and answered,” Lloyd says.

Technology, as one would expect, features prominently in the facility’s future plans, with the aim to continue to acquire state-of-the-art instruments. However, with the challenging funding environment of the past several years, finding the capital to purchase that equipment has meant the lab has had to try new strategies.

“We have taken some creative approaches to defining partnerships with outside institutions that have functionality that we do not and, vice versa, offering functionalities that they may not that we have,” he says.

Main Microscopy and Image Analysis Tools in the AMC

Leica, Nikon, Olympus, Zeiss, Life Technologies EVOS, CRI, Definiens, Visiopharm, Media Cybernetics Image Pro Plus

One of the most interesting things going on at the AMC now involves a new business venture. “I recently started a business, a start-up out of Moffitt, which takes advantage of the intellectual property that has been created in our laboratory,” Lloyd says. “We are being funded significantly right now and we’re trying to take it to the next level, so this is a very interesting opportunity for us to be able to venture out into something a little bit different.”

Lloyd sees commercialization as key to helping the patients he sees every day on his walk. “I’ve been able to envision ways that microscopy and the kinds of work that we do in the core facility can be immediately translatable to the clinic,” he says. “Some of the kinds of patents that have come out of our lab are being commercialized to actually impact the patients.”

“Research papers and grants are important, but commercialization is also important to be able to have a real impact on our patients.”

 

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Sixth Annual Investment Confidence Report

Published: March 6, 2014

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