In this newsletter we describe how chemogenetics – a technique used by neuroscientists to manipulate specific sets of neurons – is stable enough to be used in studies of primates, such as macaques. Plus, the immune system versus cancer, and regulating human telomerase.
– Peter Rodgers, Chief Magazine Editor
Microscopy image showing fluorescent signals (bright red spots) marking telomeres in human cells (inside nucleus, blue). Image credit: Sengupta et al. (CC BY 4.0)
Chemogenetics is a powerful technique that allows neuroscientists to manipulate specific sets of neurons with designer protein receptors called DREADDs. The majority of chemogenetic experiments to date have been performed in rodents, but researchers are keen to extend this approach to nonhuman primates, such as macaques and marmosets, as their brains are more similar to human brains. However, a typical primate experiment can last for several years – compared to weeks or months for rodents – and it was not known if DREADDs would remain effective over such long periods. Now, as highlighted in this Insight article, experiments on macaques have shown that chemogenetic manipulations can remain effective for over a year and a half, making them suitable for long-term studies of primates.
Many people think of aging as a process of decline that is inevitable, but research has shown that it can be delayed by targeting certain signaling pathways, including those that help the body respond to various forms of stress. The nervous system has a central role in this phenomenon, sensing the stress and then sending signals to regulate how cells respond, which is why there is growing interest in targeting neural circuits to improve health and longevity. Now, as described in this Insight article, researchers have revealed in detail how a shortage of oxygen can, under certain conditions, extend lifespan and improve health in the roundworm C. elegans. The signals are sent from the head of the worm and are carried by a range of messenger chemicals – including tyramine, the worm’s version of adrenaline – before eventually activating an enzyme called FMO-2 in the intestine.
The end of every chromosome in the human body is protected by a region of DNA called a telomere. Every time a cell divides, these telomeres become shorter, but enzymes called telomerases can add DNA to the telomeres so that they do not become too short. In 2018 it was discovered that a protein called TRF2 helps relay information about telomere length to various genes, but many of the details of this process remained unclear. Now, as explained in a paper published in eLife, researchers have shown that this information is relayed by a previously unknown feedback system involving TRF2 and a component of telomerase called TERT. A better understanding of these processes will help researchers working on aging, cancer and related diseases.
The ‘safety-efficiency dilemma’ is the challenge of pursuing rewards – such as food and shelter – in a way that is both efficient and free from danger. The human brain relies on two key systems to do this: the instrumental system learns from the consequences of our actions, weighing up costs and benefits to maximize outcomes, while the Pavlovian fear system generates automatic defensive responses. And when these two systems come into conflict, the brain must resolve this tension. Now, as reported in eLife, researchers have developed a model in which the fear response influences the instrumental response by an amount that depends on the level of uncertainty being faced. The researchers have also shown that this model can explain the results of virtual reality experiments in which people have to decide between approaching or withdrawing from stimuli that could lead to a mild electric shock.
The immune system is one of the first lines of defence against cancer, but cancer cells can evolve to escape or inhibit the immune system. Researchers are keen, therefore, to better understand the interactions that take place between tumours and immune cells during the formation and growth of tumours, and also during immunotherapy treatments. Now, as described in a paper published in eLife, researchers have developed a model in which random mutations in cancer cells trigger specialised immune responses. Combining results from the model with large-scale population data and detailed single-cell data should provide researchers with a better understanding of cancer-immune coevolution.
A study of faculty in the biology departments at 146 research-intensive universities in the United States has found that almost half (47%) of Assistant Professors are women, compared with just under two-fifths (38.5%) of Associate Professors, and just less than a third (30%) of Professors. David Alvarez-Ponce and James Vesper analysed data on 3721 male and 2104 female faculty at the universities. Compared with their male peers, female faculty tended to publish fewer papers per year, even after controlling for career stage and university ranking. However, the length of time taken to become a Professor was the same for the male and female faculty in the dataset.
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