Turkish Professor and His Team Make Significant Discovery

Important Discovery from Turkish Professor and Team Sleep is a necessity for all of us. But often it is a pleasure beyond necessity. Moreover, not only humans but all living organisms with a nervous system sleep. In humans, the sleep-wake cycle typically runs as 8 hours of rest and 16 hours of wakefulness. So how is sleep requirement determined? Why do we get sleepy? Although it may seem like a decision we make of our own free will, it is actually our biological clock that decides whether we sleep or stay awake. The biological clock located in the hypothalamus in the brain determines the duration of sleep, as well as the moments of falling asleep and dreaming. The expression of 50% of our genes is also controlled by this system. The most well-known purpose is to minimize metabolism during nighttime sleep and make metabolism more active while awake. What is critical here is the synchronized functioning of all organs. In other words, all organs work in the same time zone and regulate their processes accordingly. This entire system is called the biological clock or circadian rhythm. This system also has four main components: proteins named CLOCK, BMAL1, CRY and PERIOD. In mammalian cells, 24-hour control is provided by the time-dependent interaction of these four main proteins with each other. Nobel Prize winner Prof. Dr. Aziz Sancar, in a theory he previously presented in a publication, stated that "if you delete CRY in a cell where the p53 gene has mutated, the organism is protected from cancer." Prof. Dr. Halil Kavaklı, faculty member in the Chemical and Biological Engineering and Molecular Biology and Genetics Departments at Koç University, and his team decided to test this situation genetically predicted by Aziz Sancar by using the M47 molecule, which enables the deletion of CRY from the cell. Mutation of the p53 gene means a mammal develops cancer. [caption id="attachment_149106" align="aligncenter"] Prof. Dr. Halil Kavaklı and his team from the Chemical and Biological Engineering and Molecular Biology and Genetics departments[/caption] With this data, Kavaklı and his team, in experiments conducted on mice with mutated p53 genes, found that when they deleted CRY from the cell in the same animal, other genes also became activated and "apoptosis" occurred, which is one of the things cancer hates most. Apoptosis means programmed cell death. However, because cancer cells divide very rapidly and cannot die through apoptosis, the balance between life and death is disrupted, and cancer cells take control of the tissue in which they reside (see KURIOUS). In this case, if we can delete CRY in the cell despite the mutation in the p53 gene that causes cancer, other oncogenes (genes with high likelihood of causing cancer) trigger apoptosis in cancerous cells, and these cells die. One of the most important findings of the research is that the discovered molecule reduces the half-life of CRY inside the cell. In other words, the molecule can rapidly remove CRY from inside the cell. This means that this molecule could eliminate the effect of the mutant p53 gene, which is the cause of nearly half of known cancer types. Of course, finding this molecule was not easy. For this, they scanned a molecular library consisting of hundreds of millions of molecules with computer assistance and finally found the molecule with the desired properties. The team discovered the molecule and completed in vitro and preclinical studies; M47 molecule showed a good pharmacokinetic profile at non-toxic doses and protected mice against cancer in the event of p53 mutation. They determined that when p53 mutant mice were exposed to the M47 molecule, there was a 25% increase in their lifespan. Now they have started studies in mice to see the effectiveness of this molecule especially in pancreatic and liver cancer, which have very high mortality rates. The next step is to obtain approval from the FDA (US Food and Drug Administration). The way to do this is through having the research conducted in your own laboratories also conducted in an independent laboratory and reaching the same results. If you can successfully pass this, the FDA approves Phase 1 study, the first step of the transition from laboratory to volunteers. However, these processes require considerable financial support; accredited independent laboratories unfortunately do not exist in our country. Running these tests is also not cheap. Now it is a matter of finding an investor and taking these steps. Cancer is one of the hottest topics in the scientific world and subjects under the largest research efforts. There are very promising and successful studies. Prof. Dr. Halil Kavaklı and his team are signing on to a tremendous research that could perhaps change the "destiny" of humanity and even all animals: For the first time, they have led to the idea that a molecule that identifies a new target in the fight against cancer and deletes this target inside the cell could be used in cancer treatments. Perhaps with this research, which could yield historic results, we are once again and very powerfully filled with hope.  

What if the biological clock goes wrong?

The circadian system is considered a higher-order system; it controls the functioning of all systems in our body in a time-dependent manner. For this reason, any disorder in the circadian system can lead to numerous diseases depending on genetic background. First, in the 1960s, it was observed that night-shift nurses and flight attendants flying intercontinental flights had more than 10 times higher rates of breast cancer. It was found that in those who had to be awake during hours when they should be sleeping, a mismatch between internal and external clocks occurred. This condition can lead to breast cancer in women in particular and prostate cancer in men. If the sense of time in the cell disappears, that is, if there is a disorder in the circadian rhythm, the system will surely start to falter. For example, in mice without CRY or BMAL1, very rapid aging is observed and survival rates are very low. In a study involving Dr. Kavaklı, a mutation detected in CRY was associated with attention deficit. When Kavaklı and his team characterized a mutation in CRY, they identified delayed degradation of CRY (it does not degrade). If the molecule they found can accelerate the breakdown of mutant CRY, it could also provide a cure for attention deficit disorder caused by this mutation.   Source