AAV: Versatile Viral Hero or Neurotoxic Villain?

Review written by Amy Ciceu (NEU, 2024)

Adeno-associated viruses (AAVs) are some of the most widely used recombinant viral technologies—those that combine different genes to produce unique viral vectors, or tools that convey genetic material into cells—in modern neuroscience. Because they are incapable of being replicated within cells, recombinant AAVs are commonly used in neuroscience research as a means of expressing genes in specific cells. By expressing genes that heighten or dampen the function of certain cells, researchers are able to identify the functions of particular neural circuits.1  This approach can provide scientists with insight into the mechanisms underlying neurobiological processes. To make such circuit-related discoveries, AAVs are typically injected into certain brain regions of animal subjects. After an incubation period, some AAVs encoding fluorescent tracers can induce cells to fluoresce under specialized microscopes, enabling scientists to visualize particular neural circuitry. Furthermore, AAVs have demonstrated clinical potential; for example, AAVs have been used to replenish certain proteins in the treatment of diseases like congenital blindness 2, 3 and spinal muscular atrophy.4, 5 AAV is also currently being investigated as a potential means of treating other brain disorders, including Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), and more.6

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What other species can teach us about how infants learn to speak

Review written by Sarah McFann (CBE, G6)

One thing that sets humans apart from our closest evolutionary relatives, Old World apes and monkeys, is that much of human brain development occurs outside the womb. This means that, relative to our evolutionary neighbors, humans are born altricial—a term describing animals that are born helpless and dependent upon parental care. Because our immature brains are presented with real-world stimuli as they develop, humans have the chance to be molded by external cues like language.

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Topology helps slime bacteria form fruiting bodies

Review written by Qiwei Yu (G1, QCB)

Nature never ceases to amaze us, particularly when it comes to how biological organisms develop sophisticated and diverse strategies to survive dynamic and oftentimes hostile environments. Myxobacteria (also known as “slime bacteria”), for example, have evolved a specialized life cycle to cope with the possibility of unreliable nutrient supply. While nutrient abundance enables the bacteria to grow and proliferate, nutrient scarcity can conversely trigger a transition to a more dormant state. In response to nutrient depletion, myxobacteria cells can aggregate into fruiting bodies, three-dimensional multicellular structures of diverse colors and shapes. A subset of the cells within the fruiting bodies develop into rounded myxospores with thick cell walls, waiting for a more favorable environment to resume growth. It is truly amazing how the behavior of a large number of cells can be coordinated to achieve the rapid and dynamic process of fruiting body formation.

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A Sea Squirt Story: What our squishy relatives teach us about the origins of the vertebrate brain

Review written by Jarome Ali (EEB, G4)

Clinging to the side of a marina you might find the usual suspects like mussels and barnacles, but lurking among these life forms is a less familiar one, a squishy invertebrate that looks like nothing more than a translucent tube. This creature is the sea squirt, Ciona instestinalis. Despite its unassuming appearance, Ciona could hold the key to understanding how the brain--the most complex structure in the universe--came to be. By investigating the evolutionary origin of the brain, we can uncover the roots of the remarkable variety of intelligence in the animal world and gain a deeper appreciation for the beautifully complex human brain. Princeton researchers are now studying the simple ‘brain’ of the sea squirt to begin to unravel this evolutionary story. 

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Controlling microbial growth with a light switch

Review written by Olivia Duddy (MOL, G5)

Microbes are powerful tools in the biotechnology industry. Like microscopic factories, microbes are employed to manufacture a diversity of chemical compounds, such as industrial chemicals, food products, drugs, and other biotechnology molecules, on a large scale. Given the ease of genetic engineering in microbes like Escherichia coli and Saccharomyces cerevisiae, scientists and metabolic engineers alike tinker with their metabolic capacities, or even completely rewire them, to yield high concentrations of a specific product [1]. Metabolic engineers aim to maximize the efficiency of these biosynthetic processes. High efficiency, in turn, delivers biomolecules that are more readily available and at a lower cost. Metabolic engineering applications also can be more sustainable or environmentally friendly than traditional chemical synthesis approaches [1,2]. Recently, a team of researchers in the Avalos lab, led by former Ph.D. candidate Makoto Lalwani (now postdoctoral researcher at the Wyss Institute), added an additional layer of genetic engineering to this process: They are using light as a strategy to advance biomolecule production [3].

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Exploring the role of ADP-Ribosylation in DNA repair

Review written by Jessi Hennacy (MOL, G5)

Preserving the integrity of DNA is crucial to maintaining a cell’s functions and life cycle. However, DNA is regularly under attack by chemical and physical agents, such as toxins and UV rays from the sun, that can cause breaks in the chemical backbone that holds a strand of DNA together. This DNA damage can lead to dire consequences if left unaddressed, with effects ranging from cell death to uncontrolled cellular proliferation, which leads to cancer. Thankfully, our cells have evolved mechanisms of repairing broken DNA in order to alleviate the risks of accumulating DNA damage.  

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Understanding the entirety of the Vibrio cholerae biofilm lifecycle: First insights into biofilm dispersal

Review written by Kimberly Sabsay (QCB, G2)

Individual cells go through life cycles, in which they grow and prepare for cell division. Similarly, in certain bacteria, groups of cells go through a synergistic cycle involving the formation and disassembly of biofilms. Biofilms are essentially groups of cells that surround themselves in layers of self-made extracellular matrix proteins and polysaccharides. A biofilm is a way for cells to protect themselves from dislocation or death by predation and are present in both beneficial and pathogenic bacterial microbiomes. The sticky extracellular matrix is a structure that pathogens such as Vibrio cholerae (the bacteria that causes Cholera) can hide in to avoid detection by immune cells and thus increase their virulence. In this way, biofilms essentially provide protective armor for bacterial cells that inhibits our ability to fight pathogenic infections. 

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dSPRINT: Machine learning for uncovering protein-ligand interaction sites

Review written by Sara Geraghty (QCB, G3)

Proteins are ubiquitous in our cells. Currently, it’s estimated that the human body contains between 80,000 and 400,000 protein molecules, all busily performing the many tasks that keep your cells running smoothly and ultimately go into making you. Not only do proteins form the structural framework of your cells, but they also protect your body against foreign pathogens, help digest your food, and send and transmit signals around your body. However, they don’t do this in isolation: proteins are constantly working hand-in-hand with other proteins and molecules in your body, like your DNA, RNA, small molecules, and ions. When your DNA is replicated, or an ion is actively transported, the proteins doing the job need to recognize those molecules (and often bind to them) in order to carry out their task properly. This fundamental process of a protein binding to a partner molecule, or ligand, is critically important in biological processes ranging from development to cancer. And yet, we know surprisingly little about what proteins bind what ligands, and where -- knowledge that is key in understanding, and possibly manipulating, the inner workings of cells.

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How the egg drives its own development

Review written by Olivia Duddy (MOL, G4)

How do animals produce a healthy egg cell? To answer this, many developmental biologists investigate the complex choreography of factors required for successful egg cell development, called oogenesis. This process is crucial to the survival and reproduction of many vertebrate and invertebrate species and, remarkably, diverse species often employ a common strategy where the growth of the egg cell is supported by an interconnected network of germline, or reproductive, cells. Like cellular factories, the job of the germline cells is to produce and export nutrients to the egg via connecting cytoplasmic canals. The nutrients these support cells supply to the egg include proteins and the nucleic acids that code for them, called RNA transcripts. 

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Newborn mice form memories of their mothers that last a lifetime

Review written by Amy Ciceu (2024) & Adelaide Minerva (PNI, G2)

As youngsters, we develop memories of and connections to our parents, who nurture us throughout not only our childhoods but also much of our lives. These memories and relationships play vital roles in teaching us how to navigate the world. Do other animals form similar memories? A recent study published by the Gould Lab in Princeton’s departments of Psychology and Neuroscience discovered that mouse pups form memories of their maternal caregivers within days of birth and that these memories endure as the pups age into adulthood. 

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