Breaking News
January 21, 2018 - Youth with shared residency after parents’ divorce have less mental issues
January 21, 2018 - Sleep Better, Lose Weight? – Drugs.com MedNews
January 21, 2018 - More $$ Needed for Health Emergencies, Senators Told
January 21, 2018 - Gene test to predict breast cancer recurrence less cost effective in real world practice
January 21, 2018 - Study finds rise in number of adolescents receiving psychiatric or neurodevelopmental diagnosis
January 21, 2018 - Reminders can improve immunization rates
January 21, 2018 - A More Personalized Approach to PSA Screening in 2017
January 21, 2018 - T-cells engineered to outsmart tumors induce clinical responses in relapsed Hodgkin lymphoma
January 21, 2018 - Tetraphase Pharmaceuticals Announces Submission of New Drug Application to FDA for Eravacycline for the Treatment of Complicated Intra-Abdominal Infections (cIAI)
January 21, 2018 - Have Robotics Had a Detrimental Effect on Surgical Residency?
January 21, 2018 - Being bilingual may help autistic children
January 21, 2018 - Metrics Are Not Widespread in Rheumatoid Care
January 21, 2018 - Neuroanatomic abnormalities ID’d in those at risk for autism
January 21, 2018 - Children born with Down’s syndrome have superior genome that compensates for disability
January 21, 2018 - Study finds higher risks for asymptomatic paroxysmal AF patients
January 21, 2018 - The Second Stage of Diet Resolutions
January 21, 2018 - CT Scans Reduce Lung Cancer Deaths … But Among Whom?
January 21, 2018 - ADHD drug use soars among young women
January 21, 2018 - Researchers propose new regulation mechanism linked to action of SirT6 on chromatin
January 21, 2018 - Statins appear to reduce risk of repeated surgery in patients who undergo vitrectomy
January 21, 2018 - Morning Break: Hep A Outbreak Spreads; Tide Pod Challenge; Keeping Lobsters Out of Hot Water
January 21, 2018 - EULAR and ACR present SLE classification criteria at the 2017 ACR/ARHP Annual Meeting
January 21, 2018 - Progenics Pharmaceuticals Announces FDA Acceptance of New Drug Application for Azedra (iobenguane I 131) in Pheochromocytoma and Paraganglioma
January 21, 2018 - House Passes Funding Bill with 6-Year CHIP Renewal
January 21, 2018 - DASH ranked Best Diet Overall for eighth year in a row by U.S. News and World Report
January 21, 2018 - Dementia study sheds light on how damage spreads through brain
January 20, 2018 - Morning Break: Missing Maria Deaths; N.J. Doc Charged in Wife’s Murder; Viva Vaseline!
January 20, 2018 - No interventions proven to prevent late-life dementia
January 20, 2018 - Judge orders new Olympus trial over superbug death
January 20, 2018 - Don’t Rely on Just One Blood Pressure Test for Kids: Study
January 20, 2018 - Going Off the Deep End About Water
January 20, 2018 - Parental attention can reduce risk of drug abuse in adolescence
January 20, 2018 - Mast Uri System offers efficient and cost-friendly diagnostic solution
January 20, 2018 - International SOS, Chatham House sign partnership agreement to further advance Global Health Security Agenda
January 20, 2018 - Study offers way to predict onset of lung disease in children with cystic fibrosis
January 20, 2018 - C-Suite Must Lead in Ending Sexual Harassment
January 20, 2018 - Researchers find a way to ‘starve’ cancer
January 20, 2018 - Applied math can help predict genesis and evolution of different cancers
January 20, 2018 - UCLA researchers describe herpes virus structure associated with Kaposi’s sarcoma
January 20, 2018 - New study enrolls first patient to evaluate potential of WaveCrest LAAO System
January 20, 2018 - New review explores effects of exposing developing brains to general anesthesia
January 20, 2018 - GW Pharmaceuticals Announces Acceptance of NDA Filing for Epidiolex (cannabidiol) in the treatment of Lennox-Gastaut syndrome and Dravet syndrome
January 20, 2018 - Weight-Loss Surgery Approaches Offer Similar Results
January 20, 2018 - Free online access to millions of documents on chemical toxicity
January 20, 2018 - CE marked MAST Toxoreagent kit for detection of Toxoplasma antibodies
January 20, 2018 - DNA study sheds light on longstanding puzzle of cell division
January 20, 2018 - Montefiore provides specialized medical care to parents of adopted children
January 20, 2018 - Enzyme discovery provides new horizon of therapeutic opportunities across disease spectrum
January 20, 2018 - New smartphone app successfully enables remote monitoring of surgical wounds
January 20, 2018 - Liquid Biopsy Shows Promise for Colon Cancer
January 20, 2018 - Surgery death rates in Africa are twice global average: study
January 20, 2018 - New isothermal amplification kit using LAMP technology
January 20, 2018 - Pretreatment improves outcomes in high-risk stage 3 melanoma, study shows
January 20, 2018 - Health Highlights: Jan. 17, 2018
January 20, 2018 - House Opioid Task Force has Big Plans for 2018
January 20, 2018 - Perfectionism among young people significantly increased since 1980s, study finds
January 20, 2018 - Evidensia Sweden orders Sectra cloud-based PACS for reviewing all medical images
January 20, 2018 - Researchers test new anti-malaria medication
January 20, 2018 - Small Joint Surgeries Drop among RA Patients
January 20, 2018 - Young people with shared residency have fewer mental problems
January 20, 2018 - Childhood physical activity may have far-reaching implications
January 20, 2018 - Overweight female kidney donors of childbearing age may have greater preeclampsia risk
January 20, 2018 - MSU scientists seek to identify brain mechanisms related to psychosis
January 20, 2018 - CBT is cost-effective treatment in primary care setting, Kaiser Permanente study finds
January 20, 2018 - Scientists find how potential new eczema treatment could also alleviate asthma
January 20, 2018 - Older hospitalized patients less likely to be tested for influenza
January 20, 2018 - Syndax Pharmaceuticals Announces Clinical Collaboration to Evaluate Entinostat in Combination with anti-PD-L1 Cancer Immunotherapy in Breast Cancer
January 20, 2018 - Endoscopes Over Microscopes in Retinal Surgery: Ophthalmology Times
January 20, 2018 - Technology not taking over children’s lives despite screen-time increase
January 20, 2018 - Study finds extensive contamination around lead battery recycling plants in 7 African countries
January 20, 2018 - Researchers develop new mathematical tool to solve genetics challenge
January 20, 2018 - Flu may pass to others through exhaled breath, study shows
January 20, 2018 - Study reveals key role of macrophages in systemic sclerosis
January 20, 2018 - Neuronal loss very limited in Alzheimer’s disease, new study shows
January 20, 2018 - Toothpaste ingredient could be employed as anti-malarial drug against drug-resistant parasites
January 20, 2018 - Research shows how travel choices affect children’s well-being and achievement in school
January 20, 2018 - Novel robot can aid treatment of rare birth defect
January 19, 2018 - TherapeuticsMD Announces Submission of New Drug Application for TX-001HR
January 19, 2018 - Fighting Infant Mortality | Medpage Today
January 19, 2018 - Researchers offer new evidence on four-year-old children’s knowledge about ecology
Scientists invent new way of folding and protecting recombinant proteins

Scientists invent new way of folding and protecting recombinant proteins

image_pdfDownload PDFimage_print

A team from the NUS Yong Loo Lin School of Medicine (NUS Medicine) has invented a fundamentally new way of folding and protecting recombinant proteins. Sourced from the rapidly expanding field of synthetic biology, this protein-in-a-protein technology can improve functional protein yields by 100-fold and protect recombinant proteins from heat, harsh chemicals and proteolysis.

The expression and stabilization of recombinant proteins is the cornerstone of the biologics and pharmaceutical industries. The costs and complexity associated with manufacturing difficult-to-fold recombinant proteins at an industrial scale are a significant limiting factor to their use in clinical and industrial applications.

The study led by Dr. Chester Drum, Assistant Professor at the Departments of Medicine and Biochemistry, NUS Medicine was published in the journal Nature Communications on 13 November 2017. Dr. Drum and colleagues engineered a 12-nanometre diameter exoshell and wrapped it around a protein of interest (POI). They showed for the first time that this technology can be used to fold and protect a variety of proteins within engineered cavities that are less than 1:10,000 the width of a human hair.

The researchers developed this protein-within-a-protein technology with the help of Archeoglobus fulgidus, a hardy bacteria that is naturally found in hydrothermal vents. These hyper-thermophilic bacteria have evolved unique solutions for protein folding and stabilization due to the extreme environments in which they live.

In particular, the researchers made use of an iron-carrying, 24-subunit protein in A. fulgidus called ferritin, whose natural function is to store and carry iron in the blood. Ferritin from A. fulgidus has two unique properties: first, four tiny pores in its shell provide small molecules access into the cavity; second, unlike human ferritin which is stable at low salt concentrations, the engineered A. fulgidus ferritin dissociates at low salt concentrations, allowing the contents of the cavity to be released by a simple pH switch from 8.0 to 5.8. Once dissociated, the POI can be released enzymatically.

To demonstrate the wide versatility of their technology, the researchers tested their exoshell technology by fusing one of the 24 ferritin subunits around three POIs with diverse properties — green fluorescent protein, horseradish peroxidase (HRP) and Renilla luciferase.

Not only did the exoshell help increase the yields of all three POIs, the researchers were also able to deliver cofactors heme and calcium, in addition to oxidizing conditions, to ensure that complex POIs such as HRP protein could fold and function properly.

Besides helping to fold the POIs correctly, the exoshells were also protective against a wide range of denaturants, including high concentration trypsin; organic solvents such as acetonitrile and methanol; and denaturants such as urea, guanidine hydrochloric acid, and heat.

“We hypothesize that the significant increase in functional protein yield may be due to the complementation between the negatively charged proteins and the positively charged exoshell internal surface. Our findings highlight the potential of using highly engineered nanometer-sized shells as a synthetic biology tool to dramatically affect the production and stability of recombinant proteins,” said Dr. Drum, who is also a consultant cardiologist at the National University Hospital and director of the Clinical Trial Innovation Lab at TLGM, A*STAR.

Recruited to the National University of Singapore in 2011, he has since received funding from the Singapore MIT Alliance for Research and Technology, National Medical Research Council, Biomedical Research Council, A*STAR and NUS Medicine.

Dr. Drum’s current research bridges the gap between basic biochemistry and clinical care. He is currently the primary investigator on a multi-institutional, 3,000-person observational trial in Singapore that studies how personalized drug metabolism affects drug response.

Source:

http://nusmedicine.nus.edu.sg/

Tagged with:

About author

Related Articles