Super-Mendelian inheritance mediated by CRISPR–Cas9

A gene drive biases the transmission of one of the two copies of a gene such that it is inherited more frequently than by random segregation. Highly efficient gene drive systems have recently been developed in insects, which leverage the sequence-targeted DNA cleavage activity of CRISPR–Cas9 and endogenous homology-directed repair mechanisms to convert heterozygous genotypes to homozygosity. If implemented in laboratory rodents, similar systems would enable the rapid assembly of currently impractical genotypes that involve multiple homozygous genes (for example, to model multigenic human diseases). However, such a system has not yet been demonstrated in mammals. Here  an active genetic element that encodes a guide RNA, which is embedded in the mouse tyrosinase (Tyr) gene, is used  to evaluate whether targeted gene conversion can occur when CRISPR–Cas9 is active in the early embryo or in the developing germline. Although Cas9 efficiently induces double-stranded DNA breaks in the early embryo and male germline, these breaks are not corrected by homology-directed repair. By contrast, Cas9 expression limited to the female germline induces double-stranded breaks that are corrected by homology-directed repair, which copies the active genetic element from the donor to the receiver chromosome and increases its rate of inheritance in the next generation. These results demonstrate the feasibility of CRISPR–Cas9-mediated systems that bias inheritance of desired alleles in mice and that have the potential to transform the use of rodent models in basic and biomedical research.

http://www.nature.com/articles/s41586-019-0875-2

Plants fight fungi using kiwellin proteins

Fungal pathogens of plants  often secrete proteins that aid growth and reproduction in the host. These are termed effector proteins, and some are deregulated metabolic enzymes that manipulate key metabolic pathways in plants. A new protein has been identified in maize which  blocks the enzymatic activity of a fungal effector enzyme, thereby thwarting the effector’s ability to influence maize metabolism in a way that limits the plant’s defence response.

For more details: https://www.nature.com/articles/d41586-019-00092-2

INTRONS HELP TO OVERCOME STARVATION

Introns are ubiquitous features of all eukaryotic cells. Introns need to be removed from nascent messenger RNA through the process of splicing to produce functional proteins.Physical presence of introns in the genome promotes cell survival under starvation conditions. A systematic deletion set of all known introns in budding yeast genes indicates that, in most cases, cells with an intron deletion are impaired when nutrients are depleted. This effect of introns on growth is not linked to the expression of the host gene, and was reproduced even when translation of the host mRNA was blocked. Transcriptomic and genetic analyses indicate that introns promote resistance to starvation by enhancing the repression of ribosomal protein genes that are downstream of the nutrient-sensing TORC1 and PKA pathways.

www.nature.com/articles/s41586-018-0859-7?fbclid=IwAR3GQJDf7E_qBhZ6zKLjnhLipzubL7pxfsXbyJhaAz42MYyPTfYyJe08vJQ

Bacteria Live in Brain Cells

BACTERIA IN BRAIN

Images of human brain slices reveal bacteria, shown here to the left of a blood vessel—tantalizing but preliminary evidence of a “brain microbiome.”
https://www.sciencemag.org/news/2018/11/do-gut-bacteria-make-second-home-our-brains

Cross-talk between alternate polyadenylation and miRNA

3′ UTRs play important roles in the gene regulation network via their influence on mRNA stability, translational efficiency, and subcellular localization. For a given gene, 3′ UTRs of different lengths generated by alternative polyadenylation (APA) may result in functional differences in regulation. The mechanistic details of how length changes of 3′ UTRs alter gene function remain unclear. By combining APA sequencing and polysome profiling, we observed that mRNA isoforms with shorter 3′ UTRs were bound with more polysomes in six cell lines but not in NIH3T3 cells, suggesting that changing 3′ UTRs to shorter isoforms may lead to a higher gene translational efficiency. By interfering with the expression of TNRC6A and analyzing AGO2-PAR-CLIP data, we revealed that the APA effect on translational efficiency was mainly regulated by miRNAs, and this regulation was cell cycle dependent. The discrepancy between NIH3T3 and other cell lines was due to contact inhibition of NIH3T3. Thus, the crosstalk between APA and miRNAs may be needed for the regulation of protein translational efficiency.

For Details visit: https://genome.cshlp.org/content/28/11/1656.full.pdf+html

Cancer Moonshot initiative on Cancer Genomics

You are aware that cancer is the second most deadly disease killing  thousands of people daily. As  cancer is a complex disease application of high throughput genomics methods opens up new avenues for understanding and treating the disease.  Cancer genomics programme is   moving to the next level because of the initiatives made by Cancer Moonshot Programme (Click here to read more about Cancer Moon Shot Programme). As part of the US-Cancer Moonshot and the US-President’s Precision Medicine Initiative, Foundation Medicine is more than doubling the total number of patients represented within the NCI's Genomic Data Commons (GDC), bringing its total to over 32,000 patients accumulated in just over a month.  At its launch in early June, the GDC already shared more than five petabytes of raw unprocessed genomic data from large research projects on nearly thirty tumor types from more than 14,000 patients, along with associated clinical data (e.g. clinical diagnosis, treatment history, survival data), creating a foundational system for broad sharing and analysis of cancer genomic data, which is critical for advancing the field of precision medicine and improving the care of cancer patients.

Why I want to discuss about climate change now ?:

There is a real possibility of Donald Trump becoming US president. He does not believe in climate change. Read his views below:


"Well, first of all, I’m not a believer in global warming. And I’m not a believer in man-made global warming. It could be warming, and it’s going to start to cool at some point. And you know, in the early, in the 1920s, people talked about global cooling. I don’t know if you know that or not. They thought the Earth was cooling. Now, it’s global warming. And actually, we’ve had times where the weather wasn’t working out, so they changed it to extreme weather, and they have all different names, you know, so that it fits the bill. But the problem we have, and if you look at our energy costs, and all of the things that we’re doing to solve a problem that I don’t think in any major fashion exists. I mean, Obama thinks it’s the number one problem of the world today. And I think it’s very low on the list. So I am not a believer, and I will, unless somebody can prove something to me, I believe there’s weather. I believe there’s change, and I believe it goes up and it goes down, and it goes up again. And it changes depending on years and centuries, but I am not a believer, and we have much bigger problems. You know, I talk about global warming. You know, to me, the worst global warming, and I mentioned this to you once before, is nuclear warming. That’s our global warming. That’s what I see, because we have incompetent people, and we have these rogue nations, and not even rogue nations anymore. You know, we had a case where Vladimir Putin about three months ago threw out the nuke word. And I never thought I’d hear that from a Russia. But he said they’d better, essentially, they’d better be careful, because you know, we are a nuclear nation. That was a hell of a statement for him to make. And that’s a statement that’s made because of a lack of respect."


If this is the belief of the future US president what happens to the Paris Agreement. He might scrap the agreement. If he becomes US president the world may be in trouble. I will post soon Scientific evidences available on current climate change