Understanding mitochondrial metabolism may change how Alzheimer’s disease is identified and treated. Sarah Flowers, a neuroscientist at the University of Virginia, measures oxygen consumption to understand what is happening in brain cells.

         

Why are oxygen consumption measurements important in Alzheimer’s disease research?

Treating Alzheimer’s disease after the onset of amyloid and tau protein accumulation is difficult. However, a metabolism deficit occurs in the brain before protein accumulation, and this could be a target for early intervention. As such, we are interested in how mitochondrial metabolism is affected by Alzheimer’s disease risk factors or in Alzheimer’s disease itself. We focus specifically on oxygen consumption in astrocytes because they are the metabolic drivers of the brain.

What technical challenges are there for measuring oxygen consumption?

A lot of technologies are good for measuring different parameters at a single timepoint, but we were looking for something that could evaluate longitudinal cellular responses. We found the Resipher instrument, which can monitor samples and measure oxygen consumption over weeks and months. Importantly, it integrated with our cell culture system—we did not have to change our media, plates, or incubators. This was vital because metabolism is affected by so many things, and so it was critical for us to measure oxygen consumption in cells in their normal environments.

How has the ability to make longitudinal measurements affected your research?

We know that apolipoprotein E (APOE) genotype influences anti-Alzheimer’s drug effectiveness. Our experiments show that some therapeutics are more helpful with the APOE3 genotype while others are more useful against the APOE4 variant. By understanding the fundamental differences between these genotypes, we hope to enable more personalized, targeted therapeutics. I think these avenues of investigation are opening up possibilities for therapeutics that might be helpful at very early stages of Alzheimer’s disease.  

Learn more about longitudinal measurements of oxygen consumption.

This interview has been condensed and edited for clarity.

What obstacles do you face when trying to measure cellular metabolism?

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Tail wagging is a familiar and endearing dog behavior and is often interpreted as a sign of happiness or friendliness. However, Giulia Cimarelli, who studies canine communication at the University of Veterinary Medicine Vienna, pointed out, “This behavior as a whole is communicative…but one needs to look at the details to interpret it and really understand it.” Despite ongoing research, the reasons behind tail wagging remain a bit of a ruff mystery.

Some researchers believe the nature of tail wagging might indicate different things. A dog’s tail is an extension of its spine and is likely controlled by the cerebellum, which governs motor functions through subtle variations in position and speed. Studies suggest brain lateralization in dogs, with rightward tail wagging in response to positive stimuli, like seeing their owner, and leftward wagging for negative stimuli, such as encountering an unfamiliar dog or aggressive situation.¹ Arousal-related hormones and neurotransmitters can also influence a dog’s emotional state.²

Another, and more common, theory is that tail wagging may have emerged as a by-product during domestication, with selection for friendliness shaping tail behavior. One study found that, despite identical upbringing, dog pups showed more communicative behaviors, such as tail wagging, than wolf pups.³ Wolf pups exhibited more aggressive behavior, even toward familiar faces. However, Cimarelli and her colleagues also suggest a new hypothesis in which humans might have directly selected for this ubiquitous behavior, as the human brain is drawn to rhythmic stimuli like tail wagging.²

While this behavior may vary among breeds and dogs with docked tails, Cimarelli hopes that advanced noninvasive imaging and tracking tools will help doggedly determined researchers decode the nuances of tail wagging.

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Polymerase chain reaction (PCR) is a powerful and ubiquitously used technique for amplifying genetic material for a multitude of research, diagnostic, and therapeutic applications.¹ High quality instrumentation is key to performing accurate and reliable PCR assays. The PCR machine, also referred to as a thermal cycler, is an essential laboratory benchtop device that precisely controls temperature over a period of time. Scientists seek thermal cyclers that support the various steps of the PCR workflow and enable flexibility and throughput across different applications and uses, including PCR amplification, genotyping, sequencing, cloning, and mutagenesis.

         

Choosing the right thermal cycler can be a daunting task. Among the considerations are the goal of the PCR reaction, thermal performance, the number of users, sample throughput, device flexibility, automation features, and customer support. These decision points help guide scientists towards deciding on the ideal instrument to purchase according to their individual laboratory’s unique goals. However, oftentimes researchers face competing or changing needs, which can complicate selecting the ideal instrument.

As laboratories increasingly pursue interdisciplinary research, scientists seek instruments that can support a wider range of applications, with better reliability, longevity, and potential for integration into automated workflows. For example, Bio-Rad’s PTC Tempo Thermal Cycler provides a flexible, accurate, reliable, robust, and automated solution for streamlining a wide range of PCR workflows. With expanded connectivity, network drive access, secure user mode features, automation compatibility, and superior thermal performance, this instrument is modern and reliable. Its intuitive interface eases use for protocol management and its thermal gradient takes the guesswork out of assay optimization. 

Learn more about the PTC Tempo Thermal Cycler.

What is the most significant bottleneck in your PCR workflows?

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