Nature: toremifene is expected to be an anti-Ebola drug

Fatal infections caused by Ebola virus (EBOV) break out frequently in recent years, and Ebola outbreak in West Africa caused a large number of deaths. There are no approved effective drugs or vaccines against EBOV. Since 2013, scientists have adopted a large number of small molecules and marketed drugs in vitro mouse model tests and computer virtual screening to find compounds of anti EBOV. In 2013, Johansen, LM et al., conducted experiments on a series of selective estrogen receptor modulators including anticancer drug toremifene, finding that they have potential inhibitory effect on EBOV virus. But they did not clarify the mechanism.

Recently, David I. Stuart and other researchers from the University of Oxford took EBOV outer membrane glycoprotein (GP) as the study object and found that toremifene can combine GP and reduce its stability, thereby blocking viral fusion with the endosomal membrane and playing anti-viral effect. They also resolved the crystal structure of GP protein and the complex of GP protein, toremifene and ibuprofen, clarifying the action mechanism of toremifene.

EBOV outer membrane has a three-glycoproteins (GP, furin protein is cut into two subunits GP1 and GP2), which is solely responsible for host cell attachment, fusion kernel entry and film. Thus, GP is the primary target for the development of antiviral drugs. The researchers used recombinant protein - recombinant EBOV outer membrane glycoprotein (GP) to test whether the nine compounds would bind directly to proteins through the method of protein thermal transfer. Experimental results showed that when the dose of toremifene was 100 μM and pH value was 5.2, it can significantly reduce the melting temperature (Tm) of EBOV GP to 14 ℃. This is opposite to the previously-reported research result that inhibitors reducing the melting temperature of proteins will increase the stability of protein structure. In contrast, ibuprofen showed only a very critical effect (Tm decrease rate was less than 2 ℃), lacking for potential virus inhibition.

The researchers also first reported EBOV GP protein with no ligand and high-resolution crystal structure of the GP and toremifene and ibuprofen complex. Surprisingly, toremifene and ibuprofen all combined in a hole between the subunits GP1 and GP2. This hole is located in a huge tunnel entrance, and this big tunnel can be connected with other similar tunnels. The interactions of drug and GP1, GP2 are mainly hydrophobic effect. In filamentous virus, amino acid residues which combine with these drugs are highly conserved, excepting Marburg virus (MARV), indicating that the Marburg virus probably will not be combined with these drugs. This work illustrates the suppression mechanism of drugs on viruses, providing a viable direction for the development of more anti-EBOV drugs. Flarebio Biotech LLC is a National High-Tech Enterprise with research, production and sales as one. And high-quality recombinant proteins such as recombinant NRG3 are offered at competitive prices.

The great advantages of prokaryotic expression system for recombinant proteins

Prokaryotic expression system is developing well and the process is simple and fast. It has the advantages of low cost and high yield and is worthy trying for most proteins. It is especially suitable for eukaryotic proteins which express prokaryotic sources and don't require post-translational modification.

The necessary host bacteria of prokaryotic expression system include E.coli, Bacillus and the like. Wherein the Gram-positive Bacillus is more suitable to secrete and express recombinant proteins such as recombinant human proteins in its periplasmic space; gram-negative E.coli is capable of expressing heterologous proteins at broad spectrum.

E. coli expression system is currently the most developed recombinant protein expression system. Common strains of E. coli include BL21 (DE3), BL21 (DE3) Star, and B834 (DE3) and so on. All these strains were knocked out protease and are lysogenic to phage DE3. DE3 is a derivative λ phage with a phage resistance zone 21 and / ac / gene, / acUV5 promoter and T7 RNA polymerase gene. This section is inserted into the int gene, thus preventing DE3 from integrating into the chromosome or being excised from the chromosome in the absence of helper phage. Once forming DE3 lysogen state, only /acUV5 promoter induced by IPTG guides T7 RNA polymerase gene transcription. Add IPTG-induced T7 RNA polymerase production in lysogen culture system and then target DNA on plasmid begins to transcribe.

At the same time, there are some specially-designed strains expressing recombinant proteins with special needs. For example, methionine auxotroph expresses selenomethionine proteins; strains with enhancement of solubility express toxic protein expression strains; strains supplemented with rare codons express eukaryotic proteins. And here I would recommend a biocompany named Flarebio which produces and provides superior recombinant proteins including recombinant Cdh10 at competitive prices.

Same DNA fragments can match with each other without the help of other molecules

A new study results show that without the help of other molecules, same DNA fragments can match with each other. Genes (genetic factors) are DNA fragments with genetic effect. The results showed that each encoding gene has specific properties, no matter biological properties or biological functions. However, a gene can't always keep intact. It would often show damages and need diagnosis and repair.

The repair process of encoding genes is called homologous recombination. In this process, a broken or damaged gene can be replaced as the complete DNA sequence of the same gene. Wrong interchange of genes would lead to a variety of genetic diseases such as condition progeria, an accelerated symptom of aging.

Gene repair and homologous recombination is the key to reproduction and evolution, because this restructuring process would recombine the genes we obtain from our parents together. Recombinant protein are involved in replication and gene substitution process. However, in the genetic recombination process, the protein will react spontaneously. But the researchers didn't know how homologous genes found each other at that time. In the human genome, after coiling, DNA strand forms complex gene beam, i.e. chromosome. On the chromosome, there are more than 20,000 genes. Therefore, for different DNA strands, it is not easy to find homologous genes.

Imperial College London and the US National Institutes of Health (NIH) carried out a DNA molecule experiment in 2008, and the results showed that without any outside help (i.e. without any guidance of other proteins and molecules), DNA molecules which have the same genetic code can find their pair fragment.

These results show that two relatively- short double-stranded DNA fragments would spontaneously match with the same types of DNA after being mixed randomly in a container. Professor Mara Prentiss from Harvard University also confirmed in the subsequent study that homologous double-stranded DNA can spontaneously match. Flarebio provides you with high-quality recombinant proteins including recombinant CDH4 at a competitive price.

New findings on WNT10B gene mutations help to achieve precise treatment of congenital oligodontia

Wenzhou Medical College in China recently announced that the Genome Institute of Medicine school of this school united with Peking University School of Stomatology, Zhengzhou University School of Stomatology, Beijing Anzhen Hospital, Chinese Academy of Sciences Beijing Institute of Life Sciences, American National Institutes of Maxillofacial and Oral to first discovered that WNT10B gene mutations can lead to congenital or hereditary oligodontia. The study was recently published online in the journal Human Genetics, which is a sub-Journal of the American journal Cell. The journal also published some other studies about recombinant human proteins.

The morbidity of congenital hypodontia is 1.6% -9.6%. Oligodontia means hypodontia of six or more teeth, and it is the more serious disorders of tooth agenesis. It may be associated with abnormal development of other ectodermal body tissues, which seriously affects masticatory function and maxillofacial development in patients. It is one of the most difficult clinical oral diseases.

Currently, research on the pathogenic mechanism of oligodontia is still incomplete. The research team used technologies including the technology of recombinant protein and exome sequencing technology - namely detection of the relevant part of the whole genome encodes proteins - to conduct molecular genetic analysis on more than 150 cases of patients with oligodontia. They found that about 5% of patients showed WNT10B gene mutations, which is related to oligodontia especially lateral incisors and premolars missing, including patients with autosomal dominant inheritance and sporadic oligodontia. On this basis, the researchers explained the possible mechanisms of Wnt/beta-catenin signaling pathway the WNT10B genes involve in tooth development and oligodontia. The study found that the mutations which impact WNT10B gene function damaged the regulative ability of Wnt / beta-catenin signaling pathway to downstream TCF transcription factors, significantly reducing the ability of Wnt pathway inducing teeth embryonic stem cells to differentiate into vascular endothelial cells.

It is reported that the research results expand the gene mutation spectrum of human congenital oligodontia, providing a new basis for clinical diagnosis of congenital oligodontia, improving the pathogenesis of the disease and ultimately achieving precise treatment. Flarebio also offers recombinant CDH4 of good quality.

Various new tools allow scientists to see proteins in living cells

Proteins are particularly complex molecules. They are bent and enlaced in various ways to execute reactions which cell metabolism and growth need. But how these miniature machines are integrated together to complete the cell function? With the use of recombinant protein technology, they get some answers.

Innovation is emerging. Bewersdorf team is working with two other research teams to study clickable chemical probes: SNAP-tag of New England Biolabs and HaloTag of Promega Biotech companies. These technologies include a shorter target sequence which can be encoded to the interested protein and a dye molecule which can be embedded in the target protein by a simple chemical reaction. Bewersdorf and his colleagues have demonstrated that the two technologies can make use of organic dyes to function on living cells.

While Selvin lab developed a smaller quantum dot with a diameter of approximately 9 nm. The size allows him to glide the quantum dot between nerve cells in the space of 20 to 40 nm, and signal transduction molecules transmit information to neighboring nerve cells via this place. The lab also plans to perforate the cell membrane and then quickly seal it to prevent damage to cells. "We are able to make a bacterial enzyme called streptolysin to drill a tiny hole about 5 nanometers in the cell membrane." Selvin said. This width is enough to let through a fluorescent protein and even a protein joint with antibody in order to find the target object inside the cell. After that, researchers used the unpublished methods to patch holes in 20 minutes using of recombinant horse proteins.

In addition, there are worries that the probes would interfere with the function of the target protein. While biophysicist Jie Xiao at The Johns Hopkins University has put forward an alternative method that will not damage these proteins.

Her molecules probes don't attach to the targeted after getting genetically modified. After being produced, they are immediately split by a kind of enzymes and enter a specific location of the cell membrane. This means that they no longer carry the location information of the target molecules but they are located in a position where they can accurately calculate them, and thereby obtaining accurate count of protein production. At the same time, the protein itself can function freely. This technology is called CoTrAC.

"Quantifying protein levels in living cells is very important," Xiao explained, "People often use fluorescence to indicate the relative change." But the genes she studied regulate few proteins, and it is difficult to image through super-resolution counting. In addition, subtle changes in the precise number of these proteins also can judge whether there is a change in the state of cells. To learn more about how proteins work and what kinds of recombinant proteins (such as recombinant ACSL3) there have, you can visit Flarebio’s website.

Denosumab may prevent women carrying BRCA1 mutation from suffering from breast cancer

Recently, a study published by Australian researchers in the journal Nature Medicine indicated that a drug called denosumab may prevent women carrying BRCA1 mutation from suffering from breast cancer. The real effect of it still needs more research using recombinant horse proteins and recombinant dog proteins.

Women carrying the BRCA1 gene mutation have a very high health risk, because the mutation can significantly increase the risk of suffering from invasive breast cancer and ovarian cancer. Currently, many of such women choose to have surgery to remove breast and ovarian tissue in order to fundamentally eliminate the cancer. The famous American actress Angelina Jolie is one of them. However, if we can prevent the occurrence of cancer in these high-risk women without surgery, it will undoubtedly bring a significant improvement in their quality of life.

Australian researchers precisely identified the tumor precursor cells which may be cancerous in the future by analyzing the breast tissue of BRCA1 gene mutation carriers. These pre-tumor cells are very similar to the real tumor cells. They can proliferate rapidly, and it is easy to accumulate DNA damage; these characteristics make them easy to become cancerous.

The researchers found that these tumor precursor cells all express a protein called RANKL. Then recombinant protein found its role. This discovery is an important breakthrough, because drugs which inhibit RANKL protein signaling pathway have been used in clinical practice, such as monoclonal antibody drug denosumab. Denosumab has been approved for the treatment of osteoporosis and unresectable giant cell tumor of bone. Therefore, the researchers examined the impact of this RANKL inhibitor on tumor precursor cells in breast tissue carrying BRCA1 mutation.

The results suggest that inhibition of RANKL signaling pathway can close the proliferation of tumor precursor cells in breast tissue carrying BRCA1 mutation. Meanwhile, in the mouse model, this inhibitor can slow down the occurrence of breast cancer.

"We believe that this strategy can delay or prevent the BRCA1 gene mutation carriers from suffering from breast cancer," corresponding author Professor Geoffrey Lindeman at Australia Walter and Eliza Hall Institute of Medical Research who are also interested in the development of various recombinant proteins such as recombinant Cdh26 said, "We have begun a clinical trial to further study the role of denosumab in preventing breast cancer."

The folding mechanism is a part of the genetic code

Theoretical physicists have recently identified biological sensational news: our body's genetic information is not only stored in the nucleotide sequence of the DNA and it partly depends on the way DNA folds into chromosomes. Specifically, the three-dimensional structure of DNA will determine gene expression. In fact, the biologists are already aware of the things above and with the use of recombinant proteins, and they even have found the proteins which assist to fold DNA. But now it is a bunch of physicists who for the first time reveal the true mystery and what they use are computer simulation tools.

Watson and Crick discovered the double helix structure of DNA in 1953 and determined our genetic information is stored in the base pairs composed of four basic groups - G, A, C, T. These sequences will determine which kind of protein will be produced in which cell. Some DNA in all the cells in our body is the same at first, but why they can differentiate different proteins to meet so many different organ functional needs? Our stomach cells may not produce proteins that can make the eyes brown, but they need to produce digestive enzymes. Then how does such a division mechanism work? It is a complex question which needs a lot of experiments using the technology of recombinant protein to solve out.

In the 80's, scientists found that the mechanism was controlled by the folding way of DNA inside the cells. Besides, environmental factors are also significant. For example, environmental stress can activate and silence some genes. DNA folding way determines which genes can be "read" in the cells. To make it simple, the genes folded in the most remote corner are "unreadable" and genes on the outside can be "read". In this way, different cells can determine which protein that should be synthesized to meet different needs. Prior studies have shown that the mutation ways of DNA are more than one: in addition to changing the DNA nucleotide sequence, changing DNA folding is another way. Changing the shape and the folding of DNA bases and the "read" nature, the final protein synthesis will also be affected. Recombinant KEL can show the process.

More and more scientists are doing research in this area. With the understanding of controllable DNA folding, the possibility that we can finally take advantage of it is getting a little bit larger. Related articles have been published in the academic journal PLOS ONE.

Intake of probiotics may be effective for the prevention and treatment of depression

Japan's National Medical Center compared intestinal bacteria of 43 severe depressed patients and 57 healthy people and found that the number of beneficial bacteria bifidobacteria and lactobacilli of patients with depression was significantly less than that of healthy people. The study results show that people who have less beneficial bacteria are at a higher risk of depression.

The current number of patients receiving treatment for depression is about 700,000 in Japan, and it is supposed that patients who do not receive the treatment presumably exceed the number of 3-4 times, and it is one of the main diseases which threat much to the health state of Japanese. It is generally believed that depression is caused by biological reasons such as neurotransmitter abnormalities, endocrine abnormalities and chronic inflammation, but depression is still not more understood. There are 1,000 kinds of human gut bacteria and the number is more than 100 trillion; the total weight is about 1 to 1.5 kg. These bacteria absorb nutrients, vitamins and protein synthesis from food to prevent outside pathogenic bacteria invade the body, bearing a very important task. Scientists can use the technology of recombinant protein to realize it.

The team took 43 patients with severe depression and 57 healthy people as the object of study. They gathered bifidobacteria and lactobacilli from the stool test personnel and used 16 s rRNA genes quantitative reverse transcription polymerase chain reaction (PCR) to analyze and found that the number of bifidobacteria in patients with severe depression was significantly lower than that of healthy subjects; the total number of bacteria of lactobacillus was also low. In related analysis, the percentage of patients with severe depression who were below critical value of bifidobacterium (109.53 in per gram of feces) was 49% (21/43 people), and that of healthy groups was 23% (13/57 people). The team also found that in tested subjects, the ratio of concurrent irritable bowel syndrome in patients with severe depression was significantly higher.

The research results which were published in the online edition of the journal Affective Disorder first report that a small number of bacteria may easily lead to an increased risk of depression. And the study also finds that stress-induced mental illness such as irritable bowel syndrome is also related with beneficial bacteria. Intake of probiotics such as yogurt and lactic acid drinks may be effective for the prevention and treatment of depression. Then whether some recombinant proteins such as recombinant Lrfn1 also can do some help?

The present developing situation of CRISPR/Cas9 gene editing technology

The development of genetic editing technology CRISPR / Cas9 is just like the advent of PCR technologies. It not only opened a new door for the academic community, but also be continuously concerned by the mass media. CRISPR / Cas9 gene technology can conduct modifications, knock, knock and the like at fixed point. More importantly, CRISPR can complete genetic editing with the method of high throughput. What's more, the operation is simple and the cost is low. These features make the CRISPR / Cas9 a good choice for gene editing. Therefore, MIT Technology Review called CRISPR / Cas9 technology "century invention".

The subversive role of CRISPR / Cas9 technology in the biological and medical fields naturally is sought after by the investment community, and the massive influx of capital was invested into the startup projects related to this technology. Currently, there are three companies in leading position on the market, namely Editas Medicine, Intellia Therapeutics and CRISPR Therapeutics. Over the past three years, the three companies had financed a total of more than 660 million US dollars. In addition, they also obtained more than 500 million US dollars in revenue through cooperation with Novartis, Bayer and other well-known pharmaceutical companies.

Speaking of CRISPR / Cas9, we should also mention the controversy regarding its intellectual property ownership. Relevant legal proceedings are still in progress, but no one can place a stake in the ground. Ownership of intellectual property rights in the field of high technology has never been a black or white thing. In IT industry, Apple and Samsung all accused each other of violating its intellectual property rights from each other. Similarly in the field of biotechnology, the attribution of intellectual property rights has also been accompanied by controversy. For example, to obtain the ownership of EPO (a treatment for anemia drug), Amgen and Genetics Institute went to the court in the late 1980s to compete for intellectual property rights related to recombinant protein expression. In 1989, the federal district court in Boston judged that both sides had the patent and both of them violated intellectual property rights of each other; while in 1991, the first federal appeals court overturned the judgment of the Federal District Court in Boston and granted the intellectual property rights to Amagen. Likewise, MedImmune and Genetech had also played a lawsuit for their intellectual property related to mAb (monoclonal antibody) for many years.

The protein regulation to stem cell division

Stem cells themseves have many regulatory factors that may react to signals from outside world so as to adjust their proliferation and differentiation, including regulation of proteins with cell asymmetric division and control of gene expression of nuclear factor. In addition, the number of stem cell division before terminal differentiation of stem cells is also constrainted by intracellular regulatory factors. This is called endogenous regulation.

1. Intracellular protein regulation of stem cell division:

The differentiation of Stem cells can produce new stem cells or differentiated functional cells. This differentiation asymmetry is due to the unequal distribution of the cell's own components and other surroundings. Structural proteins of cells, in particular cytoskeletal component, is very important for the cell development. As in Drosophila ovary, the regulation of asymmetric stem cell division is a organelle called shrink body containing many regulatory proteins such as membrane contractile protein and cyclin A. The combination of the shrink body and spindle body determines the part of cell differentiation, thereby making the essential ingredients that maintain the stem cell traits remain in the progeny of stem cells.

2. The regulation of transcription factor:

In vertebrates, the regulation of transcription factors to stem cell differentiation is very important. For example, in the occurrence of embryonic stem cells, the transcription factor Oct4 is required. Oct4 is a transcription factor of mammalian early embryonic cell expression, and it induces the expression of the target gene product FGF-4 and other growth factors. It can regulate the further differentiation of stem cells and the surrounding trophoblast through making use of paracrine function of growth factor. If Oct4 deleted, mutant embryos only can develop to the blastocyst stage, while the internal cells can't develop into the inner cell mass. Besides, leukemia inhibitory factor (LIF) can promote cultured mouse ES cell self-renewal, but it has no effect on human adult stem cells, indicating that transcriptional regulation between different species is not entirely consistent. Another example is that the Tcf / Lef family of transcription factors is very important for the differentiation of epithelial stem cells. Tcf / Lef is intermediate medium of the Wnt signaling pathway. When formating transcriptional complex with the β-Catenin, Tcf / Lef can promote skin cells to turn into a pluripotent state and to differentiate into hair follicles. In the industry of biology, recombinant human protein technology is developing prosperously due to the findings above.

Chinese scientists release new findings of mTORC1 protein complex

Cells would strictly control their metabolic processes to reconcile their growth and nutritional status according to nutrient levels in the environment. mTORC1 (mammalian target of rapamycin complex) is responsible for the integration of environmental and intracellular signaling and is responsible for the regulation of cell growth. mTORC1 is similar to the generation of recombinant human protein. mTORC1 dysregulation is very common in cancer, diabetes and other human diseases.

Amino acids will make mTORC1 transfer to the lysosome and activate there. People used to think that this activation is dependent on the amino acid Rag small GTPase, Ragulator complexes and v-ATPase (vacuolar H + -adenosine triphosphatase).

Research team from Fudan University and the University of California recently found that different amino acids on the regulation of mTORC1 are not the same. Leucine mTORC1 activation requires Rag GTPase, but activation of glutamine does not depend on Rag GTPase. The results were published in journal Science on January 7, and the paper's corresponding author is famous scholar professor Kun-Liang Guan.

Professor Kun-Liang Guan is mainly engaged in signal transduction regulating cell growth and tumor cell biology. He has been awarded many honors including the "MacArthur Genius Award" in United States. He is now currently a professor at the University of California, San Diego (UCSD) Department of Pharmacy, Institute of Life Sciences, Zhejiang University jointly Dean, Fudan University Biomedical Institute for Genomic Research laboratory of molecular cell Biology and PI.

The researchers knocked out cells RagA and RagB, but glutamine still allows mTORC1 to transfer to lysosomes. The study shows that this process requires v-ATPase but not Ragulator. In addition, the researchers also found that glutamine-induced activation of mTORC1 needs Arf1 GTPase to play a role.

This study reveals an mTORC1 activation cascade which is not dependent on Rag GTPase, showing the specific amino acid differences in the regulation of mTORC1. The article points out that leucine needs RagA and RagB to activate mTORC1, while glutamine doesn't need them. This difference appears to be an evolutionarily conserved regulation.

There are many cancer cell lines show increase of mTORC1 activity, and the growth of cancer cells is highly dependent on glutamine. It can be seen that mTORC1 activation induced by glutamine plays an important role in the growth of normal cells and tumor cells, was also occupied in the study and development of recombinant mouse protein.

Using computer program to analyze p28GANK protein's function in liver cancer

Gankyrin is a recently discovered oncoprotein that is a component of the 19S regulatory cap of the proteasome. It contains a 33-amino acid ankyrin repeat that forms a series of alpha helices. It plays a key role in regulating the cell cycle via protein-protein interactions with the cyclin-dependent kinase CDK4. After searching for the gene pool, the researchers found that the gene sequence of gankyrin was exactly the same with that of p28 (Nas6p) which was found in 1998 by Hori et al. Then it was named as p28GANK. Cancer gene p28GANK coded protein is a non-ATP complex enzyme that human 26S proteasome (26S Proteasome) regulating subunit 19S/PA700 complex, the nucleic acid sequence of which contained five units-arranged in series ANK repeated units, and its conserved ankyrin sequences mediate protein-protein interactions.

20S protein corpuscle in 26S proteasome is a place at which to degrade certain misfolded proteins or cell cycle proteins in vivo. It is not clear about the specific molecular mechanisms of oncoprotein P28GANK in 26S proteasome protein degradation process. Previous studies found that cancer protein P28-GANK regulates the degree of phosphorylation of Rb through direct interaction with Rb. In addition, after the binding of P28GANK and pRb, they may also promote pRb degradation through S6bATP enzymes of 26S proteasome; or pRb directly combines with the 20S nucleus of 26S proteasome to mediate its own degradation.

Through a variety of signaling pathways of P28GANK above regulation CDK4 / CyclinD1 / p16INK4a / Rb1 / E2F-1, researchers knew that the signal transduction pathway had a very important role in the development of HCC. Therefore, interventions against the pathway and related targets may be a new way of treatment of liver cancer. This study mainly focused on critical areas and amino acids of the interaction between P28GANK and Rb in the signal transduction pathway of CDK4 / CyclinD1 / p16INK4a / Rb1 / E2F-1, using computer-aided drug design program to design specificity to block combined small molecule compound and conduct its biological function identification.

This is the first time to take Rb and spatial areas and key amino acid interactions as a target to use computer-aided drug design to conduct analysis of small molecule inhibitors on hepatocellular carcinoma p28GANK signal transduction mechanism. They have selected a specific biologically active small molecule compound, small molecules that can block the binding of Rb and P28GANK and inhibit the proliferation of liver cancer cells. Scientists also like to do experiments using recombinant rat protein and recombinant horse protein. It depends on what results you need.

Tsinghua University makes great progress in the study of humanized antibody against MERS virus

So far, there have been no specific therapeutic drugs and preventive vaccines against MERS coronavirus clinically. A research team first used of protein crystallography method to resolve three-dimensional structure of the MERS coronavirus membrane protein and the receptor-binding domain of the human receptor extracellular domain of DPP4 compound, revealing the molecular mechanism of MERS coronavirus infecting cells. The researchers also further screened and got two fully human monoclonal antibody MERS-4 and MERS-27 against MERS coronavirus with high neutralizing capacity and they can effectively inhibit the infection and spread of MERS coronavirus. Recombinant protein also can be acquired in vitro and in vivo.

Its mechanism mainly interacts by blocking the receptor binding domain of a cell surface receptor. Through in-depth analysis of the structure and function, the research group revealed that two antibodies recognized viral surface membrane proteins, and the combination of these two antibodies can significantly improve the antiviral synergy and broad spectrum. This series of studies were respectively published on July 9, 2013 and April 30, 2014 in the journal Cell Research and the US Science sub-journal Science Translational Medicine published paper entitled "MERS coronavirus S protein with the human receptor surface dipeptidyl peptidase 4 composite structure" and "Potent Neutralization of MERS-CoV by Human Neutralizing Monoclonal Antibodies to the Viral Spike Glycoprotein". Internationally renowned virologist Albert Osterhaus and Dr. Bart Haagmans spoke highly of the research team's achievements in the same period of "Research Highlights" of the journal Science Translational Medicine, saying that "the humanized monoclonal antibodies they developed with neutralizing activity play an important role in the prevention and treatment of MERS coronavirus ", and "completely humanized antibody library and the screening technology cannot just be applied for the antibody research and development of anti-MERS coronavirus but also provides key platform technology and tools for research and development against other infectious agents antibodies."

Since the end of 2013, the research group has focused on research of second-generation anti-MERS coronavirus humanized monoclonal antibody MERS-4s and has made significant progress. In recent progress, they not only maintain a high affinity and neutralizing activity of the original antibody, but also made the antibody expression levels expected to increase by 10 times, laying a solid foundation for the further development of animal experiments and clinical applications. At the same time, the research group will also further optimize MERS-4s and MERS-27 antibody, and they are now constructing antibody with a double bispecific expression. Bispecific antibodies not only have efficient neutralizing activity but also can neutralize the virus mutant, and its performance in terms of broad spectrum antiviral will be significantly improved. There are also other types of proteins that play important roles in biology research, such as recombinant protein.

Chinese scientists analyse the structure of NPC1 protein for the first time

Recently, Yan Ning study group at Tsinghua University and academician Gao Fu study group at The Chinese academy of sciences microbial groups worked together to gain a high achievement. They resolved a clear structure of NPC1 protein in the world for the first time and initially revealed its work processes, thus opening a new door for intervening and treating rare genetic disorders such as "Niemann - Pick disease" and Ebola virus.

Professor Yan Ning has been systematically studying Structural biology and biochemistry in the past nine years aiming at regulation pathways of cholesterol metabolism; academician Gao Fu has been engaged in the study of Structural biology of related virus invasion mechanism of major communicable diseases including Ebola. Their collaboratively-completed research paper NPC1 protein-mediated cholesterol transport and Ebola viruses molecular mechanism was published in the journal Cell on May 26. The paper first reported 4.4 Mr Resolution frozen electron microscopic structure of human-derived cholesterol transport protein NPC1 and analyzed to explore the molecular mechanisms NPC1 and collaboration within NPC2 two proteins mediated cholesterol transport. At the same time, it provides a molecular basis for the molecular mechanism of understanding of NPC1 protein mediator Ebola viruses invading.

It is reported that "Niemann - Pick disease" is a class because of rare genetic diseases caused by metabolic aberrations of cholesterol, sphingomyelin and other lipids, and there is no effective treatment for it now. NPC1 exception is the main risk factor of type C "Niemann - Pick disease". Over the past nearly 20 years of genetic and biochemical experiments, researchers found that NPC1 protein is indispensable porter in human cells of cholesterol. If NPC1 mutations happen, it can cause abnormal accumulation of cholesterol in the lysosomes, which may lead to excessive accumulation of lipids of the patients' liver, kidney, spleen and even brain, causing organs lesions and may be fatal. To unlock the mystery of NPC1 mutation causing the unnormal metabolism of cholesterol, to obtain a clear structure NPC1 is a key step. (Want to know other recombinant protein such as Recombinant human Protein and Recombinant Rat Protein?)

According to reports, NPC1 is a membrane protein consists of 1,278 amino acids and contains 13 transmembrane helices. Because of its number of molecule is too small and it is very unstable, making use of electron microscopy to study structural biology is a great challenge. During the process of study, Yan Ning study group developed a new electron microscopy data processing method type of "random phase 3D category", thus analysing this unstable monomer membrane protein structure to 4.4 ? and preliminaryly revealing the melecular mechanism of NPC1 and NPC2 mutual identification and cholesterol transport. In addition, NPC1 is receptor of Ebola virus in human cells, playing an irreplaceable function in the invasion process of Ebola. Yan Ning study group and Gao Fu study group worked together and parsed out frozen electron microscopic structure with a resolution of 6.6 ? of NPC1 and GPcl combination, so as to provide a molecular basis of further studying NPC1 mediated Ebola viruses invading mechanism and how to undermine the recognition interface to conduct intervention.