29 research outputs found
The All-Powerful Universal Secretor: Does it Really Exist?
Heterologous expression is the practice of using microorganisms to synthesize proteins they usually do not make. It has been useful in industry to make mass quantities of vital human proteins such as insulin. One microorganism, Pichia pastoris, is a popular strain of yeast selected by many academic and industrial laboratories for expression of these heterologous proteins. To date, over 800 proteins have been successfully expressed using P. pastoris’ powerful secretory machinery. Despite this fact, there are some proteins that P. pastoris is unable to efficiently express in significant quantities. Preceding this project, mutant super-secretor strains of P. pastoris were created and found to secrete substantial amounts of β-galactosidase; their disrupted genes were identified using BLAST sequence analysis, and these genes were isolated and cloned. Our current objective is to further investigate expression levels of two proteins HRP and SLPI in super-secretor mutants LL1, AH1 and AH2, compared to the expression levels observed in wild- type strains. Our experimental data suggest that the amounts of HRP and SLPI secreted by LL1, AH1 and AH2 slightly increased. The next steps of this study will include the development of knockouts to further examine the intricacy of Pichia’s secretory mechanisms and pinpoint the key to utilizing it to its full potential—becoming a more universal secretor
The All-Powerful Universal Secretor: Does it Really Exist?
Heterologous expression is the practice of using microorganisms to synthesize proteins they usually do not make. It has been useful in industry to make mass quantities of vital human proteins such as insulin. One microorganism, Pichia pastoris, is a popular strain of yeast selected by many academic and industrial laboratories for expression of these heterologous proteins. To date, over 800 proteins have been successfully expressed using P. pastoris’ powerful secretory machinery. Despite this fact, there are some proteins that P. pastoris is unable to efficiently express in significant quantities. Preceding this project, mutant super-secretor strains of P. pastoris were created and found to secrete substantial amounts of β-galactosidase; their disrupted genes were identified using BLAST sequence analysis, and these genes were isolated and cloned. Our current objective is to further investigate expression levels of two proteins HRP and SLPI in super-secretor mutants LL1, AH1 and AH2, compared to the expression levels observed in wild- type strains. Our experimental data suggest that the amounts of HRP and SLPI secreted by LL1, AH1 and AH2 slightly increased. The next steps of this study will include the development of knockouts to further examine the intricacy of Pichia’s secretory mechanisms and pinpoint the key to utilizing it to its full potential—becoming a more universal secretor
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Real-world treatment patterns, costs, and outcomes in patients with AL amyloidosis: analysis of the Optum EHR and commercial claims databases
This study characterised real-world treatment patterns, clinical outcomes, and cost-of-illness in patients with light-chain (AL) amyloidosis.
Data were extracted from the US-based Optum® EHR and Clinformatics® Data Mart (claims) databases (2008-2019) for patients newly diagnosed with AL amyloidosis and who initiated anti-plasma cell therapies. Healthcare resource utilisation (HCRU) and related costs were compared across lines of therapy (LOT). Incidences of cardiac and renal failure were evaluated using the Kaplan-Meier method.
About 1347 patients (EHR, n = 776; claims, n = 571) were included. Median age was 68 years; 56.8% were male. At initial diagnosis, 33.1% and 15.1% of patients had cardiac and renal failure, respectively. Most patients received bortezomib-containing treatment in LOT1 (69%); bortezomib-cyclophosphamide-dexamethasone was most common (26%). HCRU was similar across LOTs. Mean per-patient-per-month and per-patient-per-LOT costs were 105,944 for LOT1, 95,793 for LOT2, and 128,446 for LOT3, respectively. Costs were primarily driven by anti-plasma cell therapies, outpatient visits, and hospitalisations. The 5-year cardiac and renal failure rates following initial diagnosis were 64.5% and 39.0%, respectively.
AL amyloidosis is associated with substantial costs and suboptimal outcomes, highlighting the need for new therapeutic approaches to prevent organ deterioration, and reduce disease burden
Correlation of Prostate-specific Antigen Kinetics with Overall Survival and Radiological Progression-free Survival in Metastatic Castration-sensitive Prostate Cancer Treated with Abiraterone Acetate plus Prednisone or Placebos Added to Androgen Deprivation Therapy: Post Hoc Analysis of Phase 3 LATITUDE Study
Background: LATITUDE, a randomized, double-blind trial, compared abiraterone acetate and prednisone (AAP) + androgen deprivation therapy (ADT) versus placebo (PBO) + ADT in high-risk metastatic castration-sensitive prostate cancer (mCSPC)