Breaking News
October 18, 2018 - ANTRUK’s Annual Lecture sends out message on shortage of funds for antibiotic research
October 18, 2018 - NAM special publication outlines steps to ensure interoperability of health care systems
October 18, 2018 - Novel method uses just a drop of blood to monitor effect of lung cancer therapy
October 18, 2018 - New blood test could spare cancer patients from unnecessary chemotherapy
October 18, 2018 - Training young researchers to work with data volumes arising in the health sector
October 18, 2018 - New Metrohm IC method is reliable and convenient to use for zinc oxide assay
October 18, 2018 - Global AIDS, TB fight needs more money: health fund
October 18, 2018 - Understanding the forces that cause sports concussions
October 18, 2018 - Research points to new target for treating periodontitis
October 18, 2018 - New tool improves assessment of postpartum depression symptoms
October 18, 2018 - From Biopsy to Diagnosis
October 18, 2018 - Sexual harassment and assault linked to worse physical/mental health among midlife women
October 18, 2018 - Stumped by medical school? A Q&A with a learning specialist
October 18, 2018 - Targeting immune checkpoints in microglia could reduce out-of-control neuroinflammation
October 18, 2018 - FDA Approves Talzenna (talazoparib) for gBRCAm HER2-Negative Locally Advanced or Metastatic Breast Cancer
October 18, 2018 - Sleeping Beauty technique helps identify genes responsible for NAFLD-associated liver cancer
October 18, 2018 - Many U.S. adults confused about primary care, study shows
October 18, 2018 - UC researcher focuses on light-mediated therapies to target breast cancer
October 18, 2018 - With philanthropic gifts, Stanford poised to make major advances in neurosciences | News Center
October 18, 2018 - Mice study shows antibiotics are not always necessary to cure sepsis
October 18, 2018 - Researchers discover why heart contractions are weaker in individuals with HCM
October 18, 2018 - Participation in organized sport during childhood may have long-term skeletal benefits
October 18, 2018 - Probiotic/antibiotic combination could eradicate drug-resistant bacteria
October 17, 2018 - More Socioeconomic Challenges for Hispanic Women With HIV
October 17, 2018 - 49,XXXXY syndrome – Genetics Home Reference
October 17, 2018 - Scientists uncover possible new causes of Tourette syndrome
October 17, 2018 - Girl undergoes unusual heart surgery after compassionate-use exemption | News Center
October 17, 2018 - Health Issues That Are Sometimes Mistaken for Gluten Sensitivity
October 17, 2018 - Elective induction of labor at 39 weeks may be beneficial option for women and their babies
October 17, 2018 - New smart watch algorithms can accurately monitor wearers’ sleep patterns
October 17, 2018 - Researchers demonstrate epigenetic memory transmission via sperm
October 17, 2018 - FDA, DHS announce memorandum of agreement to address cybersecurity in medical devices
October 17, 2018 - Health Tip: Know the Risks of Chicken Pox
October 17, 2018 - Immunotherapy effective against hereditary melanoma
October 17, 2018 - Researchers reveal new mechanism for how animal cells stay intact | News Center
October 17, 2018 - Alzheimer's Goes Under the Cryo-Electron Microscope
October 17, 2018 - Medicare for all? CMS chief warns program has enough problems already
October 17, 2018 - Metrohm Raman introduces Mira P handheld Raman system
October 17, 2018 - Expanding the knowledge about hippocampus to better understand cognitive deficits in MS
October 17, 2018 - Study of Nigerian breast cancer patients reveals prevalence of aggressive molecular features
October 17, 2018 - Many healthy children may have metabolic risk factors, finds study
October 17, 2018 - A new antibiotic could be a better, faster treatment for tuberculosis
October 17, 2018 - “I will not become a Robot Doctor”: A medical student vows to practice compassion
October 17, 2018 - Study findings may explain sporadic outbreaks of C. difficile infections in hospitals
October 17, 2018 - Purdue researchers develop new chemical process to find better drug ‘fits’ for patients
October 17, 2018 - Yale researchers develop way to attack RNA with small-molecule drugs
October 17, 2018 - New pragmatic study launched to understand the effectiveness of new type 2 diabetes drug
October 17, 2018 - Alnylam Announces Plan to Initiate Rolling Submission of a New Drug Application and Pursue Full Approval for Givosiran
October 17, 2018 - Nine cases of polio-like illness suspected in children in illinois
October 17, 2018 - Eisai enters into agreement with Eurofarma for development and sales of lorcaserin in 17 countries
October 17, 2018 - Patients once thought incurable can benefit from high-dose radiation therapy
October 17, 2018 - Researchers awarded grant to advance testing of experimental heroin vaccine
October 17, 2018 - Researchers examine SSRI use during pregnancy and major gestational malformations
October 17, 2018 - FDA grants Rare Pediatric Disease Designation for Immusoft’s Iduronicrin genleukocel-T
October 17, 2018 - Reliable Respiratory announces acquisition of Attleboro Area Medical Equipment
October 17, 2018 - Study reveals link between childhood abuse and higher arthritis risk in adulthood
October 17, 2018 - Research shows people over 65 are not performing enough physical activity
October 17, 2018 - FDA Approves Liletta (levonorgestrel-releasing intrauterine system) 52 mg to Prevent Pregnancy for up to Five Years
October 17, 2018 - Weight gain after smoking cessation linked to increased short-term diabetes risk
October 17, 2018 - Researchers find opportunity to control salt-sensitive hypertension without exercising
October 17, 2018 - Women not warned about cancer associated with breast implants
October 17, 2018 - Metrohm offers robust handheld Raman analyzer for Defense and Security
October 17, 2018 - Modeling Non-Numerical Data in Systems Biology
October 17, 2018 - Research aims to address health disparities in African-American men
October 17, 2018 - Human and cattle decoys trap outdoor-biting mosquitoes in malaria endemic regions
October 17, 2018 - High Circulating Prolactin Level Inversely Linked to T2DM Risk
October 17, 2018 - Study finds gene variant predisposes people to both Type 2 diabetes and low body weight
October 17, 2018 - Metrohm software products make it easy to comply with ALOCA and ALCOA+ guidelines
October 17, 2018 - Network of doctors identify the cause of 31 new conditions
October 17, 2018 - Notable improvement in brain cancer survival among younger patients but not much for elderly
October 17, 2018 - Scientists shed light on roles of transcription factors, TP63 and SOX2, in squamous cell carcinoma
October 17, 2018 - Costs of Medicare Diabetes Prevention Program may be higher than expected reimbursement
October 17, 2018 - Misuse of prescription opioids or benzodiazepines associated with suicidal thoughts
October 17, 2018 - New research seeks to address sex disparities in women’s health
October 17, 2018 - C-Section Rates Have Nearly Doubled Since 2000: Study
October 17, 2018 - Talking to Your Kids About STDs
October 17, 2018 - New classification of periodontal and peri-implant diseases and conditions
October 17, 2018 - Herbert D. Kleber, Pioneer in Addiction Treatment, Dies at 84
October 17, 2018 - Health effects of smoke-filled atmosphere
October 17, 2018 - Down syndrome may hold important clues to onset of Alzheimer’s disease
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