Fighting Cancer and Aging with Telomere Research

ACRF Telomere Analysis Centre (ATAC) supports medical and biological research projects with ZEISS microscopes

Customer Story

Scott Page at the ACRF/ATAC Facility. Courtesy of CMRI/ATAC.
Scott Page at the ACRF/ATAC Facility. Courtesy of CMRI/ATAC.

The Children’s Medical Research Institute (CMRI) in Westmead (a suburb of Sydney) opened a new research center for telomeres on 21 May 2015. The Australian Cancer Research Foundation Telomere Analysis Centre (ATAC) focuses on the study of telomeres, the structures at chromosome ends, and their roles in cell proliferation, cancer and aging with the aim of supporting medical and biological research projects.
ATAC is funded with a $2 million grant from the Australian Cancer Research Foundation (ACRF) and is also supported by the Ian Potter Foundation. Several new widefield and confocal state-of-the-art microscope systems from ZEISS allow researchers at the core facility to analyze the length of telomeres, to automate scans for metaphase cells and telomeres, and to perform high-resolution fluorescence microscopy and live cell imaging.

 

Tracy Bryan, Head of the Cell Biology Unit at CMRI, is thankful for the grant to buy microscopes for the new center. “This allows us to look at telomeres in the cell with a level of detail that was not possible before.” Pragathi Masamsetti, PhD student, adds: “With our new ZEISS microscopes we can actually see if there is a DNA damage marker that goes to telomeres.” Masamsetti is working in the Genome Integrity research group, led by Tony Cesare. In 2015 the Cesare Lab published an article in Nature magazine about the functions of p53 and telomeres in cell death that was featured on the cover.

Furthermore an image showing telomeres of human metaphase chromosomes visualized by CO-FISH was featured on the cover of the November issue of Nature Structural & Molecular Biology. Tony’s current research shows how early-stage tumor cells need to overcome two barriers before becoming cancerous. “Because we understand that hurdle, we can actually target it to kill cancer cells,” Cesare explains. In his research he uses ZEISS microscopes with MetaSystems software and automation solutions.
ATAC offers a base for collaborative telomere research for scientists from a broad range of scientific and medical backgrounds and skill sets including clinical hematology, medical oncology and laboratory-based research. This is the key to the success of the center. The knowledge amassed in the several research units will be transferred from the lab to the hospital to treat childhood diseases.

Live cell microscopy of human cells (greyscale) that have been engineered to produce different fluorescent proteins at different points of the cell division cycle (red and green nuclei). Differential interference contrast and fluorescence microscopy using a ZEISS Axio Observer.Z1. Courtesy of Dr. Inmaculada Matilla, CMRI.
Live cell microscopy of human cells (greyscale) that have been engineered to produce different fluorescent proteins at different points of the cell division cycle (red and green nuclei). Differential interference contrast and fluorescence microscopy using a ZEISS Axio Observer.Z1. Courtesy of Dr. Inmaculada Matilla, CMRI.

But what makes telomeres so important in science? Telomeres are repetitive stretches of DNA found at the ends of chromosomes. They protect chromosomes from loss of crucial sequences during DNA replication, which cannot copy the very ends of linear DNA. Telomeres also prevent chromosomes from being seen as DNA damage and fusing. If telomeres become too short, cells can no longer divide and so become inactive or die. An enzyme called telomerase can lengthen telomeres by adding more of the repetitive DNA. Cancer cells use telomerase to keep growing. This knowledge can be used to find new treatments for cancer. Moreover it is known that the length of telomeres in normal cells is linked to aging, although scientists are not sure whether short telomeres are a sign of aging or a cause.

 

Interview with Scott Page, ACRF/ATAC Facility Manager

Scott Page, Director of the ATAC facility. Courtesy of CMRI/ATAC.
Scott Page, Director of the ATAC facility. Courtesy of CMRI/ATAC.

What is the biggest research question that the Children’s Medical Research Institute (CMRI) faces today?

The CMRI is recognized internationally for its research programs, focusing on four main areas: neurobiology, cancer, embryology and birth defects, and gene therapy. There are big questions being addressed in all of these areas at CMRI. One of these big questions is whether we can find ways to slow or stop cancer growth by disabling mechanisms that cancer cells use to escape the normal limits on proliferation. Almost all cancers activate mechanisms that maintain the structures at chromosome ends called telomeres, which would otherwise shorten and eventually trigger a shutdown of the cell cycle. ATAC was established to support telomere researchers by providing specialised imaging equipment to work toward answering this and other research questions about telomeres in cancer, aging, and group of rare diseases called short telomere syndromes.

“Researchers that push their research forward using the latest microscope technologies tend to have a deep interest and understanding of those technologies.”

Chromosomes (blue DNA stain) from a human cell with compromised telomeres showing DNA damage (red foci) at telomeres (green dots). Fluorescence microscopy using MetaSystems Metafer4 software on a ZEISS Axio Imager.Z2. Courtesy of Ronnie Low, CMRI/ATAC.
Chromosomes (blue DNA stain) from a human cell with compromised telomeres showing DNA damage (red foci) at telomeres (green dots). Fluorescence microscopy using MetaSystems Metafer4 software on a ZEISS Axio Imager.Z2. Courtesy of Ronnie Low, CMRI/ATAC.

Where do you see an advanced imaging facility fitting in and assisting with your areas of research?

As an advanced imaging facility, ATAC can provide the instrumentation, training and support to researchers who are embarking on new lines of research. ATAC supports research on telomeres and cancer, but will eventually assist with a broad range of research projects. CMRI has perhaps the largest number of telomere researchers at any one place in the world. This group of researchers believe that advanced microscopy techniques including live cell imaging and super-resolution will allow them to overcome a number of technical difficulties that are currently limiting major progress in the telomere field, in which fixed cell analysis and molecular techniques are more commonly used. For example, telomeres are known to be dynamic structures and the live cell imaging capabilities at ATAC will be critically important in deciphering telomere activity in the three-dimensional environment of the nucleus.

How has the uptake of the new technology been received by the users?

As part of establishing ATAC, some of the technology we acquired was familiar to the users and some of the technology was completely new. This has allowed many of the researchers to begin using some of the new instruments very quickly and easily, so they remain productive while learning more about the instruments and features that are new to them. New technology, like ZEISS LSM 880 with Airyscan has been very popular with a small group of users which is growing as more researchers begin to imagine the experiments that are now possible using the instruments.

Cultured cancer cells stained for DNA to show brightly stained chromosomes in dividing cells and round nuclei in non-dividing cells. Fluorescence microscopy using a ZEISS Axio Imager.Z2 with ApoTome.2. Courtes of Dr. Sonja Frölich, CMRI/ATAC.
Cultured cancer cells
stained for DNA to show brightly stained chromosomes in dividing cells and round nuclei in non-dividing cells. Fluorescence microscopy
using a ZEISS Axio Imager.Z2 with ApoTome.2. Courtes of Dr. Sonja Frölich, CMRI/ATAC.

What is the most important aspect to consider when introducing new technology into existing research teams and processes?

Training, in two ways. Firstly, training is needed to ensure that those who intend to use the new technology have an understanding of the theory and practical know-how to use the instruments effectively and safely. Secondly, but also importantly, is the need to train people who are accustomed to an existing procedure or protocol to accept the idea that changes to their procedures may be needed to use the new technology to its fullest extent.

Do you have any advice for aspiring researchers wishing to advance their fields of research through leading-edge microscope technologies?

My advice would be to learn as much as you can about microscopy techniques. Strive to understand how the technologies work, meaning everything from sample prep, to the microscope components, to image processing and analysis. Researchers that push their research forward using the latest microscope technologies tend to have a deep interest and understanding of those technologies. This allows them to optimize their techniques to fully exploit the technology or, when that’s not enough, develop new technology of their own.

 

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All media courtesy of the Children’s Medical Research Institute (CMRI), Westmead, Australia. ZEISS wishes to express our gratitude to our partners at the ACRF/ATAC facility and the Cesare Lab for contributing to this article and generally making the world a better place by fighting cancer and saving children’s lives. This is the moment we work for.

 

Tags: Airyscan, Confocal Microscopy, Light Microscopy

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