Genome-Wide CRISPR Screening: Putting Death on Hold

We share this planet with approximately 8.7 million species of plants and animals. Within such a diverse environment, it’s only natural that many complex relationships have developed among different species. Some relationships are mutually beneficial, some are parasitic—and some are lethal.

Natural toxins and venoms are biologically active compounds produced by normal metabolic processes in an organism but are harmful to other organisms. Typically, toxins are encountered passively or ingested by the affected organisms, and have a specific mode of action and binding site within a cell. In contrast, venoms are introduced directly into the victim through a specialized delivery mechanism, and they may consist of a mixture of compounds that affect a range of cell types and tissues (1). Both types of poisons are produced for predation, defense, or to offer a competitive advantage (1).

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Cell Tracking Using HaloTag: Why are Scientists Chasing Cells?

Cells, commonly considered the smallest unit of life, provide structure and function for all living things (3).

Eye of a fruit fly, Drosophila melanogaster, scanning electron microscopy. Scientists used HaloTag for cell tracking during eye development.
Eye of a fruit fly, Drosophila melanogaster, scanning electron microscopy

Because cells contain the fundamental molecules of life, in some situations such as yeast, a single cell can be considered the complete organism. In other situations, for more complex multicellular organisms, a multitude of cells can mature and acquire different, specialized functions (3).

Cells developing specificity are undergoing differentiation, a process where a cell’s genes are either turned “on” or “off” resultant in a more specific cell type. As these differentiated cells start to exhibit their identity, they organize themselves into the tissues, organs, and organ systems integral to the functioning of a multicellular, developing organism. This process in which order and form is created within a developing organism is referred to as morphogenesis (5).

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PARP and DDR Pathways: Targeting the DNA Damage Response for Cancer Treatment

Our cells, and the DNA they contain, are under constant attack from external factors such as ionizing radiation, ultraviolet light and environmental toxins. Internal cellular processes can also generate metabolites, such as reactive oxygen species, that damage DNA. In most cases, DNA damage results in permanent changes to DNA molecules, including DNA mismatches, single-strand breaks (SSBs), double-strand breaks (DSBs), crosslinking, or chemical alteration of bases or sugars. If left unchecked, DNA damage can cause genome instability, mutations and aberrant transcription, and oncogenic transformation.

PARP DDR pathway for drug discovery

Fortunately, our cells have also evolved multiple pathways to repair damaged DNA, collectively known as the DNA damage response (DDR). The type of repair mechanism depends on the nature of the damage, and whether the damage occurs in mitochondrial or nuclear DNA. These mechanisms have been reviewed extensively (1,2). Recently, considerable attention has focused on pathways for repairing SSBs and DSBs, mediated by the ADP-ribosylating enzyme known as poly (ADP-ribose) polymerase 1, or PARP-1.

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T Cells Newly Discovered Role in Alzheimer’s and Related Diseases Could Offer Another Therapeutic Approach

Alzheimer’s disease is a devastating, progressive degenerative brain condition that starts with mild   dementia symptoms like memory issues and gradually worsens to the point where you can no longer communicate or care for yourself. For anyone with personal experience with it, Alzheimer’s looms like a specter over the natural process of aging.

In the beginning phase of Alzheimer’s, abnormal plaques of the protein, amyloid-β, develop. These protein clumps can accumulate for decades with no detectable impact on cognitive ability or brain health. Eventually, a second protein, tau, begins to gather and form intercellular, fibrous, tangles. It is with the formation of these tau tangles that symptoms first appear. The combined presence of these extracellular plaques and intercellular tangles are the hallmarks of Alzheimer’s disease.

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Conversations: Nerve-Tumor Crosstalk in the Tumor Microenvironment

Cancer cells are characterized by features such as metabolic reprogramming and uncontrolled proliferation all of which are supported by underlying genomic instability, inflammation and the tumor microenvironment.

Cancer cells can be distinguished from normal cells by a variety of features including their ability to inappropriately activate signals for cell proliferation, evade growth suppression from contact inhibition or tumor suppressor activity, evade cell death signals, replicate DNA continually, induce angiogenesis, invade new tissues, reprogram their metabolism to provide energy for rapid proliferation, and evade immune detection (1) . Several biological processes are responsible for these features including genomic instability, inflammation, and the creation of a tumor microenvironment.

The tumor microenvironment is the network of non-malignant cells, connective tissue and blood vessels that surround and infiltrate the tumor. These surrounding “normal” cells interact with each other and the cancer cells and are important players in tumorigenesis. One cell type that is often found in the tumor microenvironment are nerve cells. In fact, cancer cells often express proteins that encourage nerve growth into the tumor microenvironment such as growth factors and axon-guidance molecules (2). Crosstalk between nerve cells and tumor cells can facilitate development of several cancer types (2) including pancreatic, head and neck, oral, prostate, and colorectal cancers.

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Monoclonal Antibody (mAb) Therapy to Delay the Onset of Type 1 Diabetes

On November 18, 2022, the US Food and Drug Administration (FDA) announced the approval of the first drug to delay the onset of stage 3 type 1 diabetes (T1D). The monoclonal antibody (mAb) drug, teplizumab, was approved for use in adults and pediatric patients 8 years and older.

3D illustration of a monoclonal antibody

The road to approval has been a bumpy one for the manufacturer, Provention Bio. In 2020, the FDA rejected the application for teplizumab due to several concerns, including the small size of the clinical trial. With the current approval, based on new clinical trial results, Provention Bio confirmed a co-promotion agreement with Sanofi US. The agreement included a $35 million Sanofi equity investment in the company.

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New Vaccine for Honeybees Could Take the Sting Out of Devastating American Foulbrood Disease

Our world is a complex, interdependent system, and invertebrate pollinators such as honeybees play a pivotal role in its survival. Threats to populations numbers of pollinators like honeybees can be equated to threats to the overall health and survival of the ecosystem in which they live. Of the over 20,000 known bee species, one—the western honeybee (Apis mellifera)—acts as the single most frequent pollinator for crops worldwide (1). Found on every continent except Antarctica, the western honeybee owes its status as a top pollinator to its widespread geographic distribution, generalist foraging behavior and competence as pollinators (1).

Deadly American Foulbrood Disease

Honeybees are the most economically valuable pollinators and are threatened by several pathogens (2). Perhaps the biggest threat to honeybee colony health and survival is the bacterial disease, American Foulbrood (AFB; (3). Caused by the spore-forming, Gram+ bacteria, Paenibacillus larvae, the highly contagious AFB disease affects the young brood of colonies.  When newly hatched larvae are fed spore-contaminated food, the spores germinate and replicate causing septicemia and death. P. larvae spores are incredibly resilient and can remain viable for decades (3). Each infected larva can produce over 1 billion new spores.  Thus, a colony can produce large numbers of spores with just a few cases of symptomatic brood (4).

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Left-Handed DNA: Is That Right?

There’s a certain group of people (including this blog post author) who derive no small amount of amusement from seeing stock photos of DNA and pointing out flaws in the structure. It’s even more amusing when these photos are used in marketing by life science companies. The most common flaw: the DNA molecule is a left-handed double helix.

What does that even mean? DNA, like many organic chemicals in biology, is a chiral molecule. That is, it can exist in two structural forms that are mirror images of each other but are not superimposable (enantiomers). Just like your left and right hands are mirror images of each other, the two DNA structures are left-handed and right-handed double helices. The DNA double helix is chiral, because its building blocks (nucleotides) are chiral.

Two DNA helices that are mirror images

It can be challenging, at first glance, to tell whether an image of DNA is left-handed or right-handed. Various helpful hints are available; however, the one that I’ve found easiest to remember is described in a blog post by Professor Emeritus Larry Moran at the University of Toronto:

Imagine that the double helix is a spiral staircase, and you’re walking down the staircase. If you’re turning to the right as you descend, the DNA structure is right-handed; if turning to the left, it’s left-handed. In the image shown earlier, the DNA molecule on the right is a right-handed double helix, while its mirror image is left-handed.

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Growing Our Understanding of Rose Rosette Virus Through Reverse Genetics

Viral particle representing lethal Rose Rosette Emaravirus with red rose.

Roses, the universal symbol of love and affection, are one of the most popular ornamental flowering shrubs used by landscapers and home gardeners and account for almost half of the billion-dollar ornamental plant market. The growing prevalence of rose rosette disease poses a significant threat to these industries.  This lethal disease is caused by the Rose rosette emaravirus (RRV) and transmitted by the tiny eriophyid mite, Phyllocoptes fructiphilus. Infection by RRV results in prolific growth of clustered and bunched plant shoots (witches’ broom), malformed flowers and leaves, malformed shoots and enlarged stems and abundant leaf growth and thorniness. This excessive growth depletes the plant’s energy, eventually causing death.

Emerging and Devastating Plant Viruses of the Genus Emaravirus

RRV is a single-stranded, segmented, negative-sense RNA virus belonging to the genus Emaravirus, a relatively new genus that was established in 2012. These emerging viruses can be devastating to trees, herbaceous woody plants and vines. At Texas A&M University, Dr. Jeanmarie Verchot’s lab is working to better characterize and understand these new viruses. In addition to threatening roses, these viruses cause damage to important agriculture crops such as wheat and pigeon peas. They also endanger sensitive ecosystems when they infect plants specialized to a particular habitat, as is the case with Palo verde broom virus infection of palo verde trees of the Sonoran Desert (1).

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The Crows Have Ideas

How smart are crows? A crow stares at a mobile phone

It has become increasingly evident to scientists that the intellectual prowess of your average crow has been roundly underestimated. With remarkable skills including superior social acumen, analogical thinking and the ability to craft and use tools, crows seem to prove themselves more and more clever with every investigation into the inner workings of their small, but mighty, brains.

Most recently, new research has revealed that crows may be capable of recursion, a hallmark feature of advanced linguistic ability originally posited by Noam Chomsky in his hierarchy of grammars. Recursion in language is used to grow the complexity of sentence structure to contain, in theory, an infinite number of embedded elements or ideas. Put simply, linguistic recursion refers to the nesting of one grammatical structure, this sentence for example, within another of the same kind. Formerly thought to be a skill exclusive to primates, research like that recently published in Science Advances has challenged this assumption.

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