Lifeboat Foundation

A research team led by Professor Yuanliang ZHAI at the School of Biological Sciences, The University of Hong Kong (HKU) collaborating with Professor Ning GAO and Professor Qing LI from Peking University (PKU), as well as Professor Bik-Kwoon TYE from Cornell University, has recently made a significant breakthrough in understanding how the DNA copying machine helps pass on epigenetic information to maintain gene traits at each cell division. Understanding how this coupled mechanism could lead to new treatments for cancer and other epigenetic diseases by targeting specific changes in gene activity. Their findings have recently been published in Nature.

Background of the Research.

Our bodies are composed of many differentiated cell types. Genetic information is stored within our DNA which serves as a blueprint guiding the functions and development of our cells. However, not all parts of our DNA are active at all times. In fact, every cell type in our body contains the same DNA, but only specific portions are active, leading to distinct cellular functions. For example, identical twins share nearly identical genetic material but exhibit variations in physical characteristics, behaviours and disease susceptibility due to the influence of epigenetics. Epigenetics functions as a set of molecular switches that can turn genes on or off without altering the DNA sequence. These switches are influenced by various environmental factors, such as nutrition, stress, lifestyle, and environmental exposures.

For the first time, scientists have developed artificial nucleotides, the building blocks of DNA, with several additional properties in the laboratory. The DNA carries the genetic information of all living organisms and consists of only four different building blocks, the nucleotides. Nucleotides are composed of three distinctive parts: a sugar molecule, a phosphate group and one of the four nucleobases adenine, thymine, guanine and cytosine. The nucleotides are lined up millions of times and form the DNA double helix, similar to a spiral staircase. Scientists from the UoC’s Department of Chemistry have now shown that the structure of nucleotides can be modified to a great extent in the laboratory.

The researchers developed so-called threofuranosyl nucleic acid (TNA) with a new, additional base pair. These are the first steps on the way to fully artificial nucleic acids with enhanced chemical functionalities. The study ‘Expanding the Horizon of the Xeno Nucleic Acid Space: Threose Nucleic Acids with Increased Information Storage’ was published in the Journal of the American Chemical Society.

Artificial nucleic acids differ in structure from their originals.

Genetics of human brain development.

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Researchers at Rutgers and Emory University are gaining insights into how schizophrenia develops by studying the strongest-known genetic risk factor.

When a small portion of chromosome 3 is missing—known as 3q29 deletion syndrome—it increases the risk for schizophrenia by about 40-fold.

Researchers have now analyzed overlapping patterns of altered gene activity in two models of 3q29 deletion syndrome, including mice where the deletion has been engineered in using CRIPSR, and human brain organoids, or three-dimensional tissue cultures used to study disease. These two systems both exhibit impaired mitochondrial function. This dysfunction can cause energy shortfalls in the brain and result in psychiatric symptoms and disorders.

A time question and answer starting at 32:22 (5−6 years)

Is aging a disease that can be cured? Neil deGrasse Tyson and cohosts Chuck Nice and Gary O’Reilly discover the field of epigenetics, the Information Theory of Aging, and curing blindness for mice with Professor of Genetics at Harvard Medical School, David Sinclair.

Continue reading “Is Aging a Disease? Epigenetics with David Sinclair & Neil deGrasse Tyson” »

In the past 10 years, gene-editing and organoid culture have completely changed the process of biology. Congenital nervous system malformations are difficult to study due to their polygenic pathogenicity, the complexity of cellular and neural regions of the brain, and the dysregulation of specific neurodevelopmental processes in humans. Therefore, the combined application of CRISPR-Cas9 in organoid models may provide a technical platform for studying organ development and congenital diseases. Here, we first summarize the occurrence of congenital neurological malformations and discuss the different modeling methods of congenital nervous system malformations. After that, it focuses on using organoid to model congenital nervous system malformations. Then we summarized the application of CRISPR-Cas9 in the organoid platform to study the pathogenesis and treatment strategies of congenital nervous system malformations and finally looked forward to the future.

Keywords: organoid, CRISPR-Cas9, congenital nervous system malformation, central nervous system, 3D

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Brain organoids have become increasingly used systems allowing 3D-modeling of human brain development, evolution, and disease. To be able to make full use of these modeling systems, researchers have developed a growing toolkit of genetic modification techniques. These techniques can be applied to mature brain organoids or to the preceding embryoid bodies (EBs) and founding cells. This review will describe techniques used for transient and stable genetic modification of brain organoids and discuss their current use and respective advantages and disadvantages. Transient approaches include adeno-associated virus (AAV) and electroporation-based techniques, whereas stable genetic modification approaches make use of lentivirus (including viral stamping), transposon and CRISPR/Cas9 systems. Finally, an outlook as to likely future developments and applications regarding genetic modifications of brain organoids will be presented.

The development of brain organoids (Kadoshima et al., 2013; Lancaster et al., 2013) has opened up new ways to study brain development and evolution as well as neurodevelopmental disorders. Brain organoids are multicellular 3D structures that mimic certain aspects of the cytoarchitecture and cell-type composition of certain brain regions over a particular developmental time window (Heide et al., 2018). These structures are generated by differentiation of induced pluripotent stem cells (iPSCs) or embryonic stem cells (ESCs) into embryoid bodies followed by, or combined, with neural induction (Kadoshima et al., 2013; Lancaster et al., 2013). In principle, two different classes of brain organoid protocols can be distinguished, namely: (i) the self-patterning protocols which produce whole-brain organoids; and (ii) the pre-patterning protocols which produce brain region-specific organoids (Heide et al., 2018).

Results of DNA studies also seem to confirm the idea that optimism is an effective tool for slowing down cellular aging, of which telomere shortening is a biomarker. (Telomeres are the protective caps at the end of our chromosomes.) This research is still in progress, but the early results are informative. In 2012, Elizabeth Blackburn, who three years earlier shared a Nobel Prize for her work in discovering the enzyme that replenishes the telomere, and Elissa Epel at the University of California at San Francisco, in collaboration with other institutions, identified a correlation between pessimism and accelerated telomere shortening in a group of postmenopausal women. A pessimistic attitude, they found, may indeed be associated with shorter telomeres. Studies are moving toward larger sample sizes, but it already seems apparent that optimism and pessimism play a significant role in our health as well as in the rate of cellular senescence. More recently, in 2021, Harvard University scientists, in collaboration with Boston University and the Ospedale Maggiore in Milan, Italy, observed the telomeres of 490 elderly men in the Normative Health Study on U.S. veterans. Subjects with strongly pessimistic attitudes were associated with shorter telomeres — a further encouraging finding in the study of those mechanisms that make optimism and pessimism biologically relevant.

Optimism is thought to be genetically determined for only 25 percent of the population. For the rest, it’s the result of our social relationships or deliberate efforts to learn more positive thinking. In an interview with Jane Brody for the New York Times, Rozanski explained that “our way of thinking is habitual, unaware, so the first step is to learn to control ourselves when negative thoughts assail us and commit ourselves to change the way we look at things. We must recognize that our way of thinking is not necessarily the only way of looking at a situation. This thought alone can lower the toxic effect of negativity.” For Rozanski, optimism, like a muscle, can be trained to become stronger through positivity and gratitude, in order to replace an irrational negative thought with a positive and more reasonable one.

While the exact mechanisms remain under investigation, a growing body of research suggests that optimism plays a significant role in promoting both physical and mental well-being. Cultivating a positive outlook, then, can be a powerful tool for fostering resilience, managing stress, and potentially even enhancing longevity. By adopting practices that nurture optimism, we can empower ourselves to navigate life’s challenges with greater strength and live healthier, happier lives.

In a world’s first, surgeons at the Massachusetts General Hospital in Boston have transplanted a kidney from a gene-hacked pig into a living 62-year-old man.

Researchers are hoping the procedure could reduce our reliance on both hard-to-come-by human donor kidneys, and the expensive dialysis machines that treat kidney disease and failure.

Fortunately, the surgeons’ efforts appear to have paid off — at least for now. The pig kidney started producing urine not long after the surgery last weekend, the New York Times reports. The patient’s condition also continues to improve, according to the report.