Description

• Key Facts
• Depression is a common mental disorder.
• Globally, an estimated 5% of adults suffer from depression.
• More women are affected by depression than men.
• Depreesion can lead to suicide.
• There is effective treatment for mild, moderate and severe depression.

Depression, also referred to as major depressive disorder, is a highly prevalent and incapacitating psychiatric condition that exerts a significant burden on individuals and societies worldwide. It is characterized by persistent and pervasive feelings of profound sadness, anhedonia (loss of interest or pleasure in activities), psychomotor disturbances, disturbances in sleep and appetite, impaired concentration, and a range of emotional and physical symptoms. Depression is intricately intertwined with physical health, as many risk factors that contribute to depression, such as sedentary lifestyle or substance abuse, are also recognized as risk factors for various somatic diseases, including cardiovascular disease, cancer, diabetes, and respiratory disorders. In turn, people with these diseases may also find themselves experiencing depression due to the difficulties associated with managing their condition.

The global prevalence and severity of depression have reached alarming levels, making it a pressing public health concern. The World Health Organization (WHO) estimates that more than 264 million individuals are affected by depression worldwide, with a higher incidence observed among women. Depression not only diminishes the quality of life for those affected but also exacts a substantial economic toll through healthcare expenditures and reduced productivity.

There is a growing emphasis on the relationship between the microorganisms inhabiting the gut (gastrointestinal microbiota) and human health. The emergence of a microbiota-gut-brain axis to describe the complex networks and relationship between the gastrointestinal microbiota and host reflects the major influence this environment may have in brain health and disorders of the central nervous system (CNS). The gut microbiotaplay an important role in the treatment and prevention of anxiety and depression through stress-related neuroendocrine, autonomic, and immune pathways.

5-Hydroxytryptamine (5-HT), also known as serotonin, often referred to as the "feel-good" neurotransmitter, is involved in regulating mood, sleep, appetite, and a range of other physiological functions. Imbalances in serotonin levels, particularly a deficiency, are implicated in the pathophysiology of depression. This deficiency is thought to contribute to the symptoms of depression, including persistent sadness and the inability to experience pleasure.

Imbalances in serotonin are considered one of the key factors leading to depression. Increasing serotonin levels can directly address the root causes of the disease, improving the emotional and mental state of patients. Antidepressant medications targeting serotonin have been extensively researched and clinically proven to be highly effective in treating depression. They can alleviate depressive symptoms, improve mood swings, reduce anxiety, and address sleep issues. By alleviating depressive symptoms, serotonin-based treatment helps patients regain normal emotional and mental well-being, ultimately enhancing their quality of life. It can boost patients' energy levels, improve interpersonal relationships, and enhance their engagement in work, leisure activities, and daily life. Compared to some other antidepressant medications, serotonin-based antidepressants typically have fewer side effects. This makes them more tolerable for patients and allows for longer-term use. In comparison to psychotherapy, using serotonin-based antidepressants can lead to noticeable effects in a shorter period of time. This enables patients to recover their normal mental state more quickly and maintain stable results over the long term.

Therefore, we hope to produce serotonin through synthetic biology methods to treat depression. Through literature research and an analysis of previous team projects, we have found that expressing serotonin using symbiotic bacteria is a promising approach. The rate-limiting step in the biosynthesis pathway of serotonin involves tryptophan hydroxylase 1 (TPH1) catalyzing tryptophan to form 5-hydroxytryptophan, which is then converted to serotonin by tryptophan decarboxylase (TDC). Therefore, by expressing TPH1 in the patient's gut using symbiotic bacteria, we can assist in the treatment of depression. However, existing TPH1 parts are diverse in their gene sources, lacking coherence and comparative analysis. Thus, we aim to screen for the most effective TPH1 gene to better assist patients with dexpression. In accordance with the kinetics of enzymatic reactions modelled by Michaelis-Menten equations, the rate of a substrate-enzyme catalysis is governed by the relative affinity of this enzyme to its substrate. Hence, by predicting the binding affinity of the TPHs to the tryptophan molecule, would allow us to predict the catalytic effectiveness of the enzyme selected. From this perspective, we have selected TPH1 genes from four organisms: humans, mice, rabbits, and zebrafish. Besides humans, the other three are commonly used model organisms in current life sciences research and represent four evolutionary patterns of TPH1. We hope to purify these four proteins and compare their functional activities to select the most potent TPH1 gene.