Laureates of 2025 Young Scientist Medal

Defender or Attacker
Some molecules in the body have two faces; sometimes they protect the body against pathogens as a member of the immune system, and sometimes they themselves challenge the immune system.
Nuclear transcription factors are a group of proteins inside the nucleus that, by binding to a part of DNA, help the cell transcribe a specific piece of hereditary material and then produce proteins through the translation process. Nuclear factor kappa B (NF-κB) is a member of the nuclear transcription factor family that plays a critical and vital role in various biological processes, including immune response, inflammation, cell growth and survival. It can be said that just as the presence and activity of this factor are essential for human health, its inappropriate or excessive activation can also be threatening. This factor can be effective in the initiation and progression of inflammatory diseases, autoimmune diseases, and even malignant tumors; therefore, understanding and controlling the signaling pathways of this factor can help improve therapeutic methods. Every cell can receive messages from the environment or other cells, then process these messages, and finally regulate an appropriate response to them. This set of actions, from issuing a message to sending a response, is called a signaling pathway or cellular messaging.

Dual Pathways: Canonical and Non-canonical
In every nucleated cell of the body, all hereditary data exists, but depending on the cell type, its purpose and function, environmental conditions, and location in the body, only part of this data is transcribed and translated. In scientific terms, the transcription of a gene is called gene expression. Nuclear transcription factors play an important role in the expression of genes involved in vital physiological responses of humans. These factors can control and regulate inflammatory responses, cell proliferation and differentiation (differentiation is the process of a cell becoming specialized), cell adhesion, and apoptosis. This set of actions is carried out through two signaling pathways: canonical and non-canonical. The reason for this naming is the distinction between the response speed, structure, and function of the components, as well as the types of receptors of these two systems from one another. The canonical pathway, also called the classical pathway, was discovered and studied before the non-canonical pathway. The non-canonical pathway has components and mechanisms different from the canonical pathway and remained unknown for years. The canonical pathway is activated more rapidly. In addition, it is activated in most cells and in response to general stimuli. In contrast, the non-canonical pathway is more specialized and is activated at a slow speed in response to specific stimuli. NF-κB proteins are often sequestered in the cytoplasm by a family of inhibitors, including IkBα, which play a prominent role in the canonical pathway. Inhibitors behave like a car brake; whenever the cell overproduces or oversecretes a substance, inhibitors force the cell to stop or reduce the production of that substance. In fact, the canonical signaling pathway of nuclear factor kappa B (NF-κB) begins with the degradation and destruction of this inhibitor molecule. Then the NF-κB complex enters the nucleus and can activate several genes. This pathway regulates important physiological functions such as bone metabolism, lymphoid organogenesis—meaning the process of forming lymphoid organs such as the spleen, lymph nodes, and intestinal lymphoid tissues—the survival and maturation of a class of immune cells called B cells that secrete antibodies, and the activation of dendritic cells—these cells, like a mediator, are responsible for identifying antigens (pathogenic pieces) and, after processing, deliver these pieces to acquired immune cells (T cells). Interestingly, in this pathway, the expression of the gene encoding the IkBα inhibitor is also activated and helps maintain balance in NF-κB activity. In the non-canonical pathway, instead of destroying the IkBα inhibitor, the kappa signaling system processes the p100 protein and converts it into p52. This conversion is the basis for the expression of a distinct set of genes that can activate follicular B cells, regulatory T cells, and cancer stem cells. Follicular B cells are a class of immune system cells located in lymphoid tissues that undertake important duties. In some cases, these cells can be the origin of cancers such as follicular lymphoma; meaning that due to incorrect regulation of NF-κB, the follicular B cells, whose duty is to defend the body, themselves become cancer cells. Ultimately, it must be said that inhibiting the non-canonical kappa signaling pathway is one of the most important goals of cancer studies.

Regulating Biological Systems with Non-coding RNAs
Sepideh Mirzaei, a researcher in the field of molecular biology and cancer therapy, has dedicated part of her research to this factor. The NF-κB signaling pathway is highly conserved (has been preserved throughout evolution in different organisms without change or with very minor changes) and can control the expression of more than 400 genes. Despite the highly critical and vital role of the NF-κB transcription factor in physiological and pathological processes, the dysregulation of this factor can enhance the proliferation of cancer cells, metastasis, and drug resistance of tumor cells. Mirzaei believes that by modulating or inhibiting NF-κB, an appropriate approach can be adopted in cancer immunotherapy. She considers this pathway a suitable target for cancer treatment.
In her research, Mirzaei points to the role of non-coding RNAs (a class of RNA molecules that are not translated into proteins but play an important role in regulating cellular activities) in balancing the kappa signaling pathway. She believes that microRNAs (miRNAs), which are from non-coding RNAs and are responsible for examining and regulating gene expression, can, with dual behavior, both inhibit and induce NF-κB signaling and influence the process of growth and migration of cancer cells. Also, miRNAs can regulate the response of cancer cells to various treatments, including radiotherapy and chemotherapy. On the other hand, long non-coding RNAs (lncRNA) and circular RNAs (circRNA) can also influence tumorigenesis by modulating NF-κB signaling.

Hyperactivity at the Cellular Level Challenges the System
Sometimes an error in the regulation of a small member of the system brings the entire system into trouble. Regulating gene expression in a genetic system is essential. If a gene is continuously turned off or on, it faces the system's survival with a fundamental challenge. It is true that the activity of kappa factor, by expressing proliferation and survival genes, prevents cell death; but its hyperactivity drives the system towards tumorigenesis. The continuous activity of this factor is like a trigger that enhances the angiogenic (the ability to build new vessels from existing vessels) and metastatic (a state indicating cancer cells have spread to other tissues) potential of cancer cells; therefore, silencing this trigger with the help of non-coding RNAs can prevent cancer spread. This idea has become a foundation for the development of novel treatments based on immunotherapy.

This research shows that many anti-tumor drugs can increase the expression of suppressor miRNAs and thereby inhibit NF-κB. This finding opened a new perspective in the simultaneous use of drugs and RNAs for cancer treatment; a model in which precise molecular regulation is the key to treatment success. Mirzaei's idea is that by restoring balance to NF-κB, targeted and personalized treatments can be designed; treatments that not only inhibit tumor growth but also overcome drug resistance. Of course, it should be noted that in the treatment process, NF-κB inhibitors must be placed only near the NF-κB of cancer cells to prevent their effect on the NF-κB of normal cells.

The Tiny Heroes of Green Energy

Planet Earth is facing major challenges such as the energy crisis, climate change, and the depletion of natural resources. In the midst of this, microalgae have emerged as organisms with incredible potential for the future of energy. Although microalgae look simple, they hold remarkable abilities. According to Show Pau Loke, microalgae act like a biorefinery. This means that besides extracting biofuel from microalgae, we can also simultaneously obtain other valuable products such as pigments, proteins, lipids, carbohydrates, vitamins, and antioxidants.

More Than Meets the Eye

The substances extracted from microalgae are used in various industries, including food, pharmaceuticals, and cosmetics. Some of these compounds also help in the treatment of diseases like cancer. Specifically, microalgae lipids are suitable for producing biodiesel, while their carbohydrates can replace sugar or biomass in industrial fermentation processes. This is how the biorefinery structure takes shape—similar to an oil refinery, but instead of crude oil, it uses green, living biomass.

Challenges of Raising Tiny Heroes

Despite their high potential, working with microalgae is not simple. Cultivating and processing these organisms is expensive and requires advanced technologies. Microalgae are usually grown in open ponds or closed systems. Closed systems are like small greenhouses where environmental factors such as light, temperature, and carbon dioxide are carefully controlled. This type of monitoring leads to higher-quality production of lipids and other valuable substances.

The Magic of CO₂

To extract valuable products from microalgae, methods such as supercritical carbon dioxide extraction are used. In this method, carbon dioxide acts like a magical tool, separating valuable materials without the need for harmful chemicals. This method not only has higher efficiency but also consumes less energy.

A Fresh Look at Little Wonders

Studies conducted by Show Pau Loke show that if biofuel production is combined with the simultaneous extraction of valuable products, the entire process becomes economically and environmentally viable. Although there are challenges in the path of developing this technology, the future of this approach looks bright. Microalgae-based biorefineries could become an important part of green energy and a sustainable economy. It seems the time has come to take a different look at these tiny yet powerful organisms—they can play a big role in building a cleaner, healthier future for Earth.