For decades now, peptides have been a molecule of interest for drug discovery research. Peptides offer a unique opportunity for therapeutic intervention that closely mimics natural pathways, as many physiological functions utilize peptides as intrinsic signaling molecules. Macrocyclic peptides, in particular, have recently proven to be promising candidates for targeting intracellular protein–protein interactions (PPIs), an attractive but hard-to-reach therapeutic target for conventional small molecule and biological drugs.
As with any opportunity, there are also challenges that accompany the peptide therapeutic development. Peptide ligands typically have poor membrane permeability, so thus far the majority of peptide therapeutics predominantly target extracellular proteins and receptors. There are also multiple mechanisms for cellular uptake of peptides, including both energy-dependent routes like endocytosis, and energy-independent, like passive diffusion or membrane translocation. Multiple mechanisms of cellular uptake paired with poor permeability makes engineering enough membrane permeability into peptides in order to advance them through drug discovery pipelines extremely difficult.
There are other factors to consider in developing peptide therapeutics, such as solubility, protein/lipid binding and stability, which can also have an affect on the overall cytosolic concentration and, ultimately impact the ability of the peptide to effectively engage its desired intracellular targets.
With so many challenging factors, the ability to have a predictive, high-throughput assay to assess cell permeability, independent of the mechanism(s) of entry, would be a critical and invaluable tool to support peptide drug discovery research.
Each year, the International Forum on Consciousness draws thought leaders from around the world to explore important, and often challenging, topics related to the exploration of consciousness. The theme for this year, Consciousness of Connection: Awakening from Despair to Awe, is an invitation to broaden curiosity about connection and take a closer look at the variety of connections that we forge in our lives.
Participants will examine the kinds of connections that transcend our individual selves and reach our inner desire to be part of an interconnected world, perhaps to transform our current sense of the individual, community, and society, from independent to interdependent. More specifically, the Forum will examine connection across the primary aspects of our lives with:
Self, and the many selves in our amazing neural networks
Others, and the multiple communities we intersect
Nature, and the breadth of life forms that surround us
Although it is easy to get swept up in the dark year that was 2020, one advantage of overwhelming darkness is it makes it easier to find the bright spots, the beacons of hope, the people working to make the world a better place. One of these bright spots was the launch of Wild Genomes, a new biobanking and genome sequencing program through Revive & Restore.
Back in 2018, the Catalyst Science Fund was established by Revive & Restore with a 3-year pledge from Promega for $1 million annually. The purpose of the fund is to help support proof-of-concept projects and to advance the development of new biotechnology tools to address some of the most challenging and urgent problems in conservation that currently lack viable solutions, including genetic bottlenecks, invasive species, climate change and wildlife diseases.
Through this fund, the Wild Genomes program was launched, with the goal of getting sequencing and biobanking tools into the hands of people working to protect biodiversity right now, and to help support them in applying genomic technologies towards their wildlife conservation efforts.
In their first request for proposals , the competitive Wild Genomes program received over 58 applications from researchers in 19 different countries, all of which aimed to address various species conservation issues using applied genomic technologies. The second round of projects, to be announced this Spring, will focus solely on marine species. Take a look at these first 11 amazing projects that have been awarded funding and the species conservation challenges they are taking on below:
Canine distemper virus (CDV) is a highly contagious pathogen that is the etiological agent responsible for canine distemper (CD), a systemic disease that affects a broad spectrum of both domestic dogs and wild carnivores. While there are commercially available vaccines for CDV that can provide immunity in vivo and protect canines from contracting CD, there is a strong demand for effective canine distemper antivirals to combat outbreaks. Such drugs remain unavailable to date, largely due to the laborious, time-consuming nature of methods traditionally used for high-throughput drug screening of anti-CDV drugs in vitro. In a recent study published in Frontiers in Veterinary Science, researchers demonstrated a new tool for rapid, high-throughput screening of anti-CDV drugs: a NanoLuc® luciferase-tagged CDV.
On August 6, 2020, the first successfully cloned Przewalski’s horse was born at the Texas-based veterinary facility, Timber Creek Veterinary, along with a new hope for restoring some much-needed genetic diversity to the species. The successful birth of this foal is the culmination of the collaborative efforts between Revive & Restore, San Diego Zoo Global (SDZG), and ViaGen Equine, and lays the groundwork as an important model for future conservation efforts.
The new Przewalski’s foal (pronounced “shuh-VAL-skees”) has been affectionately dubbed Kurt, in honor of noted animal conservationist, geneticist and pathologist, Dr. Kurt Benirschke. Dr. Benirschke played an instrumental role in founding the Frozen Zoo®, a genetic library comprised of cryopreserved cell lines of endangered species. Established in the 1970s, this collection was built on a foundation of prescient hope, banking on the future development of reproductive and cloning technologies that did not yet exist.
Now thanks to his foresight, that gamble is paying off and the fruits of that labor are literally being brought to life almost 50 years later through Kurt the foal, who is as adorable as he is important to the future of his kind.
As the SARS‐CoV‐2 pandemic continues to rage across the United States and around the globe, the demand for COVID‐19 testing is increasing. The vast majority of the COVID-19 assays use RT‐qPCR to detect the viral RNA in patient samples such as nasopharyngeal swabs, which are collected and stored in viral or universal transport media (VTM/UTM). The general workflow for these COVID‐19 assays can be broken down as follows:
Collect and store patient samples
Ship samples to testing laboratory
Extract RNA from samples
Amplify and analyze samples
While many companies who manufacture the products that are used in these steps have been able to adapt and significantly increase their production capacities, there are still gaps between the supply of these products and the global test demand. Both the sample collection and storage step and the RNA extraction/purification step have a tendency to bottleneck and experience supply constraints. One way to address these bottlenecks and expand production capacity for these in‐demand products is to evaluate the viability of skipping a step in the workflow, without hindering the ability to detect viral RNA from samples.
From the beginning of this pandemic, scientists around the world have been working around the clock in pursuit of answers that can effectively combat the SARS-CoV-2 virus. One of hardest things for people to grapple with, is all the unknowns: When will this end? When can I safely visit my friends and family again? What if I have it or had it and I don’t even know it?
The increased availability of serological testing has helped ease people’s minds about their personal COVID-19 status. From a distance, serological testing may seem like a huge milestone in the marathon that is this pandemic. Unfortunately, many of these tests provide murky and inconsistent results.
The ability to target protein interactions with low solubility or weak binding affinities can present a significant challenge when it comes to drug screening. The beauty of these types of challenges we often face in the lab is that finding solutions to these problems doesn’t necessarily require brand new tools. Sometimes we already have the right tools in our arsenal and, with just a little creativity and collaboration, they can be adapted to address the challenge at hand.
In the following video, Dr. Mohamed (Soly) Ismail, a Postdoctoral Fellow at the Downward Lab of the Francis Crick Institute, presents the perfect example of this with his novel approach to the NanoBiT® Protein:Protein Interaction Assay. Through a collaboration with Promega R&D Scientists, Dr. Ismail has translated the assay into a cell-free, biochemical format, termed the NanoBiT Biochemical Assay (NBBA).
In recent years, scientists have been hot on the trail of transcription factor FOXO3, tracing its involvement in various tumor-centric activities comprising the many trademarks of cancer, from drug resistance to metastasis to tumor angiogenesis.
FOXO3 is a member of the O sub-class of the forkhead box family of transcription factors. The forkhead box (FOX) family is characterized by a fork head DNA-binding domain (DBD), comprised of around 100 amino acids. They have also proven themselves to be a family of many hats, functioning in diverse roles ranging from metabolism, immunology, cell-cycle control, development, as well as cancer (1). The forkhead box O (FOXO) sub-class alone has demonstrated involvement in a variety of cellular outcomes, from drug resistance and longevity to apoptosis induction.
Due to its pro-apoptotic and anti-proliferative proclivity, FOXO3 has been previously identified as a tumor suppressor gene. However, more and more studies have begun to flip the narrative on FOXO3, portraying it more as a devoted henchman, due to its roles in drug and radiotherapy resistance, cell-cycle arrest and long-term maintenance of leukemia-initiating stem cells in a variety of cancer types, including breast cancer, pancreatic cancer, glioblastoma, and both acute and chronic myeloid leukemia.
Cardiovascular diseases, or CVDs, are collectively the most notorious gang of cold-blooded killers threatening human lives today. These unforgiving villains, including the likes of coronary heart disease, cerebrovascular disease and pulmonary embolisms, are jointly responsible for more deaths per year than any other source, securing their seat as the number one cause of human mortality on a global scale.
One of the
trademarks of most CVDs is the thickening and stiffening of the arteries, a
condition known as atherosclerosis. Atherosclerosis is characterized by the
accumulation of cholesterol, fats and other substances, which together form
plaques in and on the artery walls. These plaques clog or narrow your arteries
until they completely block the flow of blood, and can no longer supply
sufficient blood to your tissues and organs. Or the plaques can burst, setting
off a disastrous chain reaction that begins with a blood clot, and often ends
with a heart attack or stroke.
Given the global prevalence and magnitude of this problem, there is a significant and urgent demand for better ways to treat CVDs. In a recent study published in Nature Communications, researchers at the Carnegie Institution for Science, Johns Hopkins University and Mayo Clinic are taking the fight to CVDs through the study of low-density lipoproteins (LDLs), the particles responsible for shuttling bad cholesterol throughout the bloodstream.
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