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A new compound called d16 that reduces tumor growth and overcomes treatment resistance in mutant p53-bearing cancers has been developed by researchers at the Baylor College of Medicine. Their findings testing the compound, published in the journal Cancer Research Communications, suggests the new compound could be used in combination therapies to provide more effective treatment against these kinds of cancer.
“One of the most common alterations in many human cancers are mutations in p53, a gene that normally provides one of the most powerful shields against tumor growth,” says Helena Folly-Kossi, PhD, a postdoctoral associate in Weei-Chin Lin’s lab at Baylor and the study’s first author. “Mutations that alter the normal function of p53 can promote tumor growth, cancer progression and resistance to therapy, which are associated with poor prognosis. It is important to understand how p53 mutations help cancer grow to develop therapies to counteract their effects.”
According to Lin, finding ways to target p53 mutations directly as a form of therapy for cancer has been difficult. His lab has been working for many years to not interfere directly with p53, but rather to identify vulnerabilities in the cells carrying p53 mutations that they could target to prevent cancer growth. “One of the challenges has been to develop drugs that act on mutant p53 directly. Some of these drugs are under development, but they appear to be toxic,” he said.
Researchers at Baylor College of Medicine and Rice University received a grant for more than $3.9 million over five years from the National Institutes of Health’s Office of Research Infrastructure Programs to establish the Baylor/Rice Genome Editing Testing Center (GETC). The new center will assist investigators from across the country with somatic cell genome editing experiments in mouse models.
Somatic cell genome editing, the ability to edit DNA within the body’s non-reproductive cells, is a promising potential treatment for the most severe human diseases. Over the last decade, significant effort has gone into developing more effective genome editing systems and methods of delivery to specific cells and organs. However, many of these new technologies do not progress to use in humans because there is insufficient evidence from animal models supporting their effectiveness.
“Our center will provide mouse model resources and genome editing testing pipelines to researchers who are developing new genome editing and delivery technologies but need assistance with conducting preclinical animal studies,” said Dr. Jason Heaney, co-principal investigator and associate professor of molecular and human genetics at Baylor. “Our goal is to help generate the animal model data needed to demonstrate the therapeutic potential of these cutting-edge technologies.”
The last 2 questions and the answers are great. The first starts at 30 minutes. And I like his answer to the 2nd question especially, the time is 33:54. “What is giving me great hope is that we’re entering the phases where we have more than enough tools to get really get close to escape velocity.”
Genome Engineering for Healthy Longevity – George Church at Longevity Summit Dublin 2023.
Cancer tumors hijack the genetic program used by developing nerves. This is shown in a study published in the journal Frontiers in Genetics by researchers at Umeå University. In the long term, the results may open up new ways of treating cancer by limiting the tumor’s interaction with the nerves.
“We are still only early in the research, but this opens up exciting opportunities to fight cancer in the body in a completely new way,” says Sara Wilson, associate professor of neurobiology at the Department of Integrative Medical Biology at Umeå University.
In cancer, there is an interaction between tumors and nerves. You could say that the tumor talks to the nervous system. The researchers believe that by interpreting this “conversation,” it will later be possible to find ways to break it and thus slow down the cancer or reduce the risk of it spreading.
The effect of a TE on its host can be classified analogous to the effect of point mutations. In the majority of cases, the consequences of a TE their activity (transposition to a new genomic site) is either neutral or deleterious. The latter occurs, when TEs disrupt genes and their functions, or when, they trigger de-novo genomic instability by transposition or TE-mediated chromosomal rearrangements, which can lead to disease1, 3. TEs can occasionally have a positive impact on the host genome, for example, by impacting gene regulatory networks. In the British peppered moth (Biston betularia), a TE inserted within the first intron of the cortex gene, resulted in increased transcription levels, subsequently affecting cell cycle regulation during wing-disc development through the amount of cortex protein product, resulting in the iconic melanic form4. However, more research is needed to understand these different evolutionary impacts that TEs can have when interacting with their host genome.
The increased accessibility to high throughput sequencing technologies has greatly increased our ability to analyse genetic differences caused by changes at the nucleotide level, and patterns of natural selection on coding sequences, and simultaneously allowed us to disentangle phenotypic differences at the nucleotide level. Mounting evidence has started to shed light on non-coding regions having important effects on genomic variation3. While TEs can be found in the genomes of virtually all organisms, large proportions of TEs are often absent from reference genomes, as their repetitive nature impedes their assembly and can result in collapsed regions within the reference genome2, 5. These difficulties have led to an increased demand for reference genomes that are of a higher quality and are more complete. More importantly, a new demand for high-quality annotations of non-coding regions in reference genomes has surfaced. Annotations of non-coding regions are imperative to study the evolution of these regions between and within species. Improvements in sequencing techniques, especially the addition of long-read sequencing, and improved bioinformatic analytical tools are resulting in the assembly of increasingly gapless reference genomes, enabling the curation of high-quality TE annotations.
The current efforts of large consortia, such as the VGP6 and the B10K7 to create high-quality references for a wide variety of organisms provide invaluable data to improve our endeavours for a better understanding of TEs. With these new resources we can take our research into TEs and their effects on host genomes further, for example, to better understand the evolution of complex traits across phylogenomic scales. One such a complex trait is seasonal bird migration and recent research across a migratory divide in willow warblers identified a diagnostic TE correlated with migratory direction8. Here we focus on the Eurasian blackcap (Sylvia atricapilla), another iconic model species for bird migration, and consequently, the resource published here may be able to add insight to the quest to resolve the genetic background of migratory behaviour.
A new CRISPR-based gene-editing tool has been developed which could lead to better treatments for patients with genetic disorders. The tool is an enzyme, AsCas12f, which has been modified to offer the same effectiveness but at one-third the size of the Cas9 enzyme commonly used for gene editing. The compact size means that more of it can be packed into carrier viruses and delivered into living cells, making it more efficient.
Researchers created a library of possible AsCas12f mutations and then combined selected ones to engineer an AsCas12f enzyme with 10 times more editing ability than the original unmutated type. This engineered AsCas12f has already been successfully tested in mice and has the potential to be used for new, more effective treatments for patients in the future.
By now you have probably heard of CRISPR, the gene-editing tool which enables researchers to replace and alter segments of DNA. Like genetic tailors, scientists have been experimenting with “snipping away” the genes that make mosquitoes malaria carriers, altering food crops to be more nutritious and delicious, and in recent years begun human trials to overcome some of the most challenging diseases and genetic disorders.
Ageing has always been inevitable but fasting, epigenetic reprogramming and parabiosis are just some of the scientific techniques that seem to help people stay young. Might the Peter Pan dream become real?
00:00 — Can science turn back the clock?
01:01 — Centenarians.
02:51 — What is ageing?
04:51 — Dietary restriction.
06:00 — Roundworms.
07:55 — Epigenetics.
09:43 — Blood and guts.
11:40 — Senolytics.
12:38 — Metformin.
13:51 — Anti-ageing treatments are coming.
Ribonucleic acid (RNA) is a molecule which is present in cells and made of genetic material to help build proteins necessary for cell function. RNA provides a template for the construction of proteins and is essential for cell and organism life. Immune cells rely on these proteins, including CD8+ or cytotoxic T cells which are responsible for killing invading pathogens. Importantly, cytotoxic T cells are a major component of the memory immune response. A pool of T cells specifically designed to recognize an invader is stored for future invasion of that particular pathogen. For example, once these cells are exposed to an invading antigen or protein, the immune system will expand T cells specific to that antigen and remember the antigen next time it enters the body. Vaccines work in a similar way by introducing a foreign antigen to the body, so the immune system is ready if the pathogen ever enters your body in the future. Only a small set of T cells that expand survive and it is unclear how this process occurs.
Recently a team of researchers at the University of Massachusetts Amherst (UMass) demonstrated that a single strand of RNA governs a T cells ability to recognize and kill tumors. The single strand of RNA is known as let-7 and is a microRNA, which is responsible for gene expression regulation. The recent discovery may improve vaccine development and cellular memory to enhance immunotherapy against cancers. Immunotherapy is a general term referring to cancer therapies that try to activate the immune system to kill the tumor compared to other drugs that try to directly kill the tumor with chemicals, such as chemotherapy.
The report published in Nature Communications identified that the microRNA, let-7, may enhance memory of T cells. Researchers led by Dr. Leonid Pobezinsky, Associate Professor of Veterinary and Animal Sciences at UMass, further built on our understanding of how T cells form immune memory. Pobezinsky and colleagues found that a small piece of microRNA that has been present throughout evolution is expressed in memory cells. Additionally, they found that more let-7 a cell has, the more likely that cell will recognize a cancer cell and kill it. The increased let-7 also indicates that the cell will turn into a memory cell after being exposed to an antigen. The regulation of enhanced memory T cells by let-7 is an integral process key to fight infections. This is a critical finding, especially because memory cells retain stem-like characteristics and can survive for decades.
