(Yin and) Yang in the fairytale world of science
The method was chosen as “Breakthrough of the Year” by the journal Science in 2015. It enables rapid and efficient targeting of a specific gene, or a DNA sequence, and its subsequent editing. In theory, this method could eventually treat diseases in humans.
Besides heritability, a gene can be turned on or off by a group of regulating enzymes, e.g. histone aceyltransferase (HAT) enzyme. In autumn 2016, Yang De Marinis published a study in which her research team succeeded in using CRISPR/Cas9 to remove a sequence in the genetic code which governs the function of a HAT enzyme in insulin-producing cells from rats. As a result, she observed loss of function of the HAT gene, and subsequently decreased activity of a diabetes-associated gene TXNIP. This study presented clear evidence that TXNIP, which is associated with the toxic effect of glucose in diabetes, can be turned off by HAT inactivation. The cells with HAT mutation introduced by CRISPR also had increased insulin production, and decreased cell death.
Yang De Marinis sees great potential in the application of CRISPR/Cas9 and hopes to develop further the technique within her research group at Lund University Diabetes Centre, to make it as precise and effective as possible. In pursuit of this approach, she has also established active collaborations with groups at the Broad Institute of Harvard and MIT, as well as local research teams. She believes that the method will open up opportunities to study function of unlimited number of genes, and could gradually be applied not only in basic research, but also in clinical treatment in diabetes. Such example has already been set in treatment of sickle cell anaemia, which is caused by a mutation in the red blood cells. There, researchers were able to correct the mutation from patient’s own stem cells, and later induced them into functional red blood cells. Yang De Marinis believes that it should be possible to apply similar approach in diabetes research.
“There are major challenges. But it would be a perfect scenario, and we are trying to make it work!”
Busy but encouraging parents
Yang De Marinis grew up in Inner Mongolia, a semi-autonomous province in northern China with 24 million inhabitants. Her father was a professor in developmental biology and her mother is an artist who teaches oil painting at an art academy.
“My parents have always been busy, but they made sure to open up exploring opportunities for my brother and me”, she says.
Together, the two siblings investigated and dissembled all the electronic equipment in the house – everything except the TV which they were not allowed to touch. Both went on to study electrophysics and are currently working in the field of diabetes research, Yang at Lund University Diabetes Centre and her brother at Oxford University.
“I always wanted to become a scientist. My father has been my role model, he was innovative, courageous and very academic,” Yang De Marinis says.
“My parents have always been encouraging and supportive. Me and my brother got a library card for the university library where my father worked and we went there every week. We read a lot of books on biographies, science, astronomy, Greek mythology, fairytales, and history…”
Already as a child, she has been fascinated by the mystery of nature and how everything is connected. Reading stimulated her imagination and ability to think innovatively and boundlessly, which she thinks is an advantage as a researcher. Driven by the questions of how nature creates its own patterns and balance in existence, she has devoted herself in biology and genetics, which she describes as a “scientific treasure hunting”.
“The more I study and learn, the more amazed I am about how everything can be so precise and well-balanced. You wonder who has created it? ”
It sounds almost like a religious question!
The culture background of Buddhist and Taoism philosophy where she grew up did impact her. She believes in an existence of harmonic balance, yin and yang, a little white in the black and a little black in the white. She also believes that this philosophy also applies for her current research on type 2 diabetes.
“The human body is so perfectly designed, but unfortunately when not taken care of, it can be destroyed by ourselves through over eating and junk food. This creates stress in the system. I believe some diseases such as obesity-related diabetes can be avoided if we are in harmony with ourselves.”
During the ten years that Yang De Marinis has been active in her research career, diabetes has increased from 194 million adults (2003) to 415 million people affected (2015). The prognosis for 2040 is 642 million. A clinical visit during her PhD study had a strong impact on her.
“We got to meet diabetes patients who told us their stories, the consequences of the disease, the pain and fear. We also got to see patients with complications, with amputations and lost toes… For the first time, I realized what terrible disease diabetes is because of its complications!”, she says.
In her research, she wants to contribute to increasing knowledge about the cause of diabetes, and how to prevent its complications at an earlier stage. She focuses on the effects of lifestyle on our genes and, more specifically, how high blood sugar levels affect the development of type 2 diabetes, and why some people gets complications while others don’t.
“That is my current goal. In the years to come, I want to eventually contribute to the fight against obesity. Overeating, especially eating the wrong kind of food, exposes our body to high levels of glucose and fat, and this may lead to tissues damage over time.”
But changing the behavior of a society is hard. Yang De Marinis believes in encouragement rather than punishment. The food industry also carries a major responsibility, according to her. “Diabetes causes so much suffering in patients and heavy economic burden of the society, money that we could have spent in education or helping people in other parts of the world”, she says. “We have the responsibility to change this. It is sick that one part of the world is suffering from overeating and its consequences, while the rest of the world is dying from hunger.”
She practices what she believes. She exercises every day and is disciplined in her own eating habits.
“I never buy Coca Cola and have no sugary drinks at home. I have taught my children to read the ingredient list on food packaging in the shops and encourage them to exercise.”
“After all, we should stay healthy if we are in harmony and balance with our own bodies. Exercise, good and right amount of food!”