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Ask the Expert: How to Overcome Challenges with Microscopy

Dr. Rebecca Williams, director of the Microscopy and Imaging Facility at Cornell University, talks about her role in overseeing the imaging laboratory while pursuing independent research in the field.

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Dr. Rebecca Williams, Director of the Microscopy and Imaging Facility at Cornell University, talks to Tanuja Koppal, Ph.D., contributing editor to Lab Manager about her role in overseeing the imaging laboratory while pursuing independent research in the field. She talks about how the facility functions, its users and the trends in microscopy that she has spotted in recent years.

Q: How is the Microscopy and Imaging facility at Cornell run?

A: The microscopy and imaging facility at Cornell is a user-based facility. Instruments are available for use for an hourly fee. We started out as a confocal microscopy facility and hence, fluorescence microscopy has always been our area of expertise. We have now procured a couple of other instruments such as a bioluminescence-based whole mouse imaging system and a fluorescence-based instrument that can image anything from whole animals to single cells. We also have a high-resolution ultrasound machine. We don’t have an infrared (IR)-based imaging system yet, but a number of researchers are moving towards IR-based applications. Our routine users don’t work in the IR region but a few of our biomedical engineers are developing probes for IR imaging.

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Q: Who are your users? What types of applications drive them to use your facility?

A: We have a very diverse user base but most of them are cell biologists. Some are plant researchers studying the biology of a plant cell, while others are cell biologists looking at fixed preparations or live animal cells. We also have material scientists using our facility to image all kinds of different materials and structures. The instruments remain the same but we try to accommodate each individual user as much as we can.

Q: Do you provide any kind of training to your users?

A: The Microscopy and Imaging Facility is a part of the Cornell Life Sciences Core Laboratory Center. We have two facilities. One is located in the veterinary school and is more animal (mouse)-based and the other is on the central campus, which is more cell and tissue-based. Users can use either facility depending on their needs. We are probably the only facility where the users work by themselves. Each facility has a manager who trains people on the basic use of the instrument, but imaging tends to be so specialized that you have to mostly do it yourself. Our managers are there to troubleshoot and their expertise is critical to the users as they help carry out some of the more challenging experiments. We have also had success getting people to communicate with each other. We used to have a monthly seminar series where people would come and talk about their work. They would also share tips and give advice on how to do certain things correctly.

Q: What is your role as the director of the facility?

A: My role is to accommodate the research needs of the Cornell campus. I have to make sure that things are operating smoothly and safely. I am also responsible for the overall finances of the facility. We have to keep up with new equipment that is available for new applications. When we need a new instrument, we access the need on campus and then put in for a shared instrumentation grant to the government. We just put in a grant proposal for a spinning disk confocal microscope, which allows very rapid optical sections to be obtained in a very short time period. The instruments often don’t run at cost recovery and the University has been generous in supporting these facilities to make sure we have adequate space and that the instruments are well-maintained.

Q: What trends in microscopy have you seen since you took over as director in 2007?

A: Users are now more interested in doing live cell and tissue work and they are interested in developing probes that are “smart” and indicative of biological function. The optics of confocal microscopy hasn’t changed much but the instruments have more features added on. As people are starting to use more live cells and tissues, these instruments are getting easier to buy and use. No more perfusion pumps all over the place. People are also using different imaging strategies by combining various technologies, for instance, luminescence coupled with X-rays. There are also more high-resolution optical imaging techniques being developed like stochastic optical reconstruction microscopy (STORM) and photoactivated localization microscopy (PALM).

Q: Do you have any advice for people looking to buy or upgrade their microscopy instruments?

A: My advice is to look for specific instrument characteristics that you need for your applications. For instance, in live tissue imaging, efficiency is important. We need our instrument software to be intuitive and user-friendly because the imaging here is done by the researchers themselves. Five years ago the software programs varied a lot, but now with most instruments the software is relatively straightforward and quite comparable. A relationship with the vendor is also important and technical service is a very critical feature, especially for us, since we are so remotely located. We have nearly ten imaging instruments in our facility, out of which four are confocal microscopes. We try and troubleshoot as much as we can ourselves. We also have service contracts on our two primary confocal instruments, the ones that are used all the time. For the secondary instruments we can afford a little bit of down time while they get fixed.

Q: Besides directing the imaging facility you are also pursuing your own research. Can you give us some details on that?

A: My research is funded by DRBIO, which stands for Developmental Resource for Biophysical Imaging and Optoelectronics, a NIH-funded developmental resource for optical research and instrumentation. My current research projects involve using adaptive optics to more effectively image through scattering tissue and developing probes for in vivo imaging of oxygen tension. I have been involved in developing instrumentation and applications for multiphoton microscopy since 1991. Multi-photon imaging was developed at Cornell in 1990, but is now becoming more widely used for cellular imaging and clinical applications. We have different multi-photon instruments that are in various stages of development at the DRBIO facility. This technique is suited for in vivo imaging and helps image deeper. Although the optics is simpler, it is more expensive than confocal microscopy.

Dr. Rebecca Williams is the director of the Microscopy and Imaging Facility, which is a part of the Cornell Life Sciences Core Laboratory Center. As the director, her role is to ensure that the facility is meeting the imaging needs of Cornell’s research community. She is also the associate director of DRBIO, a NIH/NIBIB optical imaging resource. She holds faculty positions at Cornell as a research scientist in the Biomedical Engineering department and as an adjunct assistant professor in the Biomedical Sciences department. She received her Ph.D. in physics from Cornell University in 1997.