Previous opinions on cancer considered cancer as driven by specific somatic mutations. However, cancer studies revealed that most cancer are not caused by specific driver mutations, but caused by complex gene networks.
We have found that the translation is globally regulated in cancer. This may serve as a signature of most cancer types. Cancer cells are able to regulate the translatome of their microenvironment and thus gain the survival and progression. Mutations may be simply a result of translatome misregulation rather than the reason. This may raise a revolution on cancer studies and therapy.
Antibiotic-resistant (AR) bacteria is becoming a major threat on public health, which causes 85% deaths of infectious diseases. It is increasingly difficult to develop new antibiotics. In contrast, the bacteria evolves resistance within one year of the clinical usage. Therefore, we try to answer the question: why can the “simple” bacteria evolve resistance against everything?
We discovered that translation regulation is a swift and common defense mechanism against most antibiotics types. Manipulation of the translation system can further tune this response. Therefore, translation system may serve as a promising target to prevent the resistance.
We are also willing to collaborate with the structural biologists and pharmaceutical scientists to design specific antibiotics against prokaryotic ribosomes to fight against the AR bacteria.
Translatome has been adaopted as one of the key resource pillar of the Human Proteome Project (HPP). As an important group in the HPP, we are still developing new methods, both experimental and computational, aiming the complete resolution of the human proteome, including the protein types (especially the protein-coding “non-coding RNAs”), sequence variants, modifications and dynamics. Most of our current ongoing work showed potential of groundbreaking advancements. Almost all of such improvements are based on the translatome-aided proteomics strategies.
Taking the advantage of our omics infrustructure and hyper-accurate algorithms, we are trying to find novel biomarkers, mainly the proteins and exosome-encapsulated nucleic acids, for the diagnosis, prognosis, monitor, etc. of complex diseases, such as cancer, cardiovascular diseases and autoimmune diseases. Using novel statistical design and accurate omics methods, we have successful experiences on the biomarkers of Kawasaki Diseases and promising results of various types of cancer. We are also cutting the cost to a very low level so that these tests may be widely and regularly performed as population-level screening.
The production of many pharmaceutical and industrial proteins in prokaryotic hosts is hindered by the insolubility of industrial expression products resulting from misfolding. Even with a correct primary sequence, an improper translation elongation rate in a heterologous expression system is an important cause of misfolding. The actual reason is that the correct amino acid sequence do not guarantee the correct folding, even in the same environment. The translational pausing, mediated by the codon selection and tRNA abundance, is an important determinant for protein folding.
Therefore, we established a novel strategy to efficiently promote the expression of soluble and active proteins without altering the amino acid sequence or expression conditions. This strategy uses the rational design of translational pausing based on structural information solely through synonymous substitutions, i.e. no change on the amino acids sequence. We demonstrated this strategy on several proteins which are hard to expressed in soluble form in wild-type sequences. We enhanced the soluble expression yield hundreds to 2000 folds, and reached even higher specific activity than the wild-type. Therefore, this strategy enables new possibilities for the efficient production of bioactive recombinant proteins.
We are the only team in the world who developed high-accuracy algorithm solutions for both next-generation sequencing and shotgun mass-spectrometry-based proteomics. We have established the world’s most powerful commercialized cloud-based omics computational platform, the “Chi-Cloud” operated by Chi-Biotech Co. Ltd., for the new era of omics research and the precision health/medicine.