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- Thalén, Niklas, 1985-, et al.
(författare)
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Systems biology greatly improve activity of secreted therapeutic sulfatase in CHO bioprocess
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Rare diseases are, despite their name, collectively common and millions of people are affected daily of conditions where treatment often is unavailable. Sulfatases are a large family of activating enzymes related to several of these diseases. Heritable genetic variations in sulfatases may lead to impaired activity and a reduced macromolecular breakdown within the lysosome, with several severe and lethal conditions as a consequence. While therapeutic options are scarce, treatment for some sulfatase deficiencies by recombinant enzyme replacement are available. However, such recombinant production of sulfatases suffers greatly from low product activity and yield, further limiting accessibility for patient groups. Here, we have addressed this problem by defining key-proteins necessary for active sulfatase secretion by comparison of CHO clones with different levels of production of active sulfatase. Quantitative transcriptomic analysis highlighted 14 key genes associated with sulfatase production, and experimental validation by co-expression improved the sulfatase enzyme activity by up to 150-fold. Furthermore, a correlation between product mRNA levels and sulfatase activity were observed and expression with lower activity promoters showed an increased in sulfatase activity. The workflow devised is general and we propose it to be useful for resolving bottlenecks in cellular machineries for improvement of cell factories for other biologics as well.
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- Thalén, Niklas, et al.
(författare)
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Tuning of CHO secretional machinery improve activity of secreted therapeutic sulfatase 150-fold
- 2024
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Ingår i: Metabolic engineering. - : Elsevier BV. - 1096-7176 .- 1096-7184. ; 81, s. 157-166
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Tidskriftsartikel (refereegranskat)abstract
- Rare diseases are, despite their name, collectively common and millions of people are affected daily of conditions where treatment often is unavailable. Sulfatases are a large family of activating enzymes related to several of these diseases. Heritable genetic variations in sulfatases may lead to impaired activity and a reduced macromolecular breakdown within the lysosome, with several severe and lethal conditions as a consequence. While therapeutic options are scarce, treatment for some sulfatase deficiencies by recombinant enzyme replacement are available. The recombinant production of such sulfatases suffers greatly from both low product activity and yield, further limiting accessibility for patient groups. To mitigate the low product activity, we have investigated cellular properties through computational evaluation of cultures with varying media conditions and comparison of two CHO clones with different levels of one active sulfatase variant. Transcriptome analysis identified 18 genes in secretory pathways correlating with increased sulfatase production. Experimental validation by upregulation of a set of three key genes improved the specific enzymatic activity at varying degree up to 150-fold in another sulfatase variant, broadcasting general production benefits. We also identified a correlation between product mRNA levels and sulfatase activity that generated an increase in sulfatase activity when expressed with a weaker promoter. Furthermore, we suggest that our proposed workflow for resolving bottlenecks in cellular machineries, to be useful for improvements of cell factories for other biologics as well.
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- Anderhag, Per, et al.
(författare)
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Syften och tillfälligheter i högstadie- och gymnasielaborationen : en studie om hur elever handlar i relation till aktivitetens mål
- 2014
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Ingår i: NorDiNa. - : University of Oslo Library. - 1504-4556 .- 1894-1257. ; 10:1, s. 63-76
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Tidskriftsartikel (refereegranskat)abstract
- Purposes and contingencies in the lower and upper secondary school labStudies have shown that students’ awareness of the goals and purposes of the laboratory activity is important for their possibility to participate in and learn from the activity. While practical activities often have been considered to be a central part of science education, relatively few studies have examined laboratory work in situ. In this paper we addressed these issues by examining (a) what purposes are distinguished when students’ work with a laboratory assignment and (b) how these purposes are made continuous with the teacher’s aim with the assignment. The data was based on classroom observations from two ordinary laboratory settings, one from a chemistry class in lower secondary school and one from a physics class in the natural science programme in upper secondary school. Although both student groups acknowledged their teacher’s intentions with the practical and could act towards the more student centered purposes of the activity, e.g. describe what happens with the copper and measure the speed of a small vessel respectively, there were differences regarding the possibilities the students had to act toward the activity’s final aim. The results showed that these factors can be referred to the amount of purposes introduced by the teacher as well as those that arose because of contingences, and the connection of these purposes to students’ prior experiences.
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- Andersson, Sebastian, et al.
(författare)
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Establishing epistemic practices in students’ formulation of scientifically researchable questions in upper secondary science education
- 2019
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Ingår i: NOFA7 ABSTRACTS Stockholm University, 13 - 15 May 2019. ; , s. 24-24
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The development of students' capability to engage in scientific inquiry is part of the science curricula across the educational system. However, previous research shows that laboratory and practical work in science education do not necessarily develop the capability to engage in scientific inquiry or contribute to developing an understanding of the nature of inquiry. The purpose of this study is to explore how teaching activities can be designed with a specific focus to develop students' capability to formulate questions for scientific inquiry. Some science education research points to that in order for students to develop an understanding of the nature of science inquiry, teaching has to include activities explicitly focusing aspects of inquiry such as asking questions, observing and making inferences. In this study we draw on the theoretical framework of epistemic practices to analyse and design teaching with the purpose of developing students' capabilities to formulate questions for scientific inquiry. Epistemic practices refer to the ways people in a specific community propose, justify, evaluate and legitimize knowledge claims within a disciplinary framework. From this perspective, formulating scientifically researchable questions makes sense only as part of epistemic practice in relation to a motive of knowledge production. The research question is: How can epistemic practices be established in upper-secondary school science where students are invited to participate in activities of formulating researchable questions?The study was carried out as a design-based research collaboration with a research team consisting of nine science teachers and four science education researchers. Data was collected in three cycles of design, intervention and analysis of research lessons with six classes in three different upper-secondary schools. The data consists of video-recordings of student interaction while engaging in tasks of formulating researchable scientific questions. The data is analysed using the didactical model of organizing purposes; distinguishing between overarching purposes and the student-orientated purposes emerging in interaction. The results indicate that the development of students’ capabilities to formulate researchable questions is situated in the processes of interaction with peers, and the conditions for situating the formulation of questions in a practice characterised by closeness to an epistemic object and gathering of observational data. Based on the results, we argue for a shift in science education from focusing students’ views of a generic nature of science or nature of science inquiry to focussing student participation in epistemic practices of various kinds.
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- Andersson, Sebastian, et al.
(författare)
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Students’ capabilities to formulate scientifically researchable questions in upper secondary science education
- 2019
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Ingår i: NOFA7 ABSTRACTS Stockholm University, 13 - 15 May 2019. ; , s. 25-25
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- A goal for science education is to develop student capabilities to participate in scientific inquiry. This includes various aspects of inquiry; formulating scientifically researchable questions as well as planning, performing, analyzing and presenting science investigations. In science education practices, there is a tradition of using practical or laboratory work to illustrate science concepts; focussing correct answers and reproduction of ready-made scientific knowledge, rather than engaging students in inquiry. Previous research shows that inquiry teaching predominantly engage students in investigating science questions as formulated beforehand by the teacher or a textbook. Little attention has been paid to what might characterize the capability of formulating scientifically researchable questions in school. In this study we draw on a theoretical framework of epistemic practices. Epistemic practices refer to the ways people in a specific community propose, justify, evaluate and legitimize knowledge claims within a disciplinary framework. From this perspective, formulating and developing scientifically researchable questions makes sense only in relation to a motive of knowledge production. The aim of this study is to explore what might characterize students’ capabilities to formulate and develop scientifically researchable questions in upper secondary science education.The collected data consists of video-recordings of student interaction in group-work focussing formulating and developing scientifically researchable questions. Data was collected as part of a design-based study with six classes in three different schools. The video-recordings were transcribed in verbatim and analysed by the means of qualitative content analysis. The preliminary results suggest three themes: Formulation of scientifically researchable questions as:1) Working with the specification of the epistemic object. The theme illustrates how the students elaborated on the meaning of related scientific concepts and discussed cause and effect. 2) Specifying researchability by focussing on how to operationalize the epistemic object. The theme illustrates how the students reformulate their questions as part of a process of discussing e.g. measurability and variables.3) Making value-judgements of epistemic objects. The theme illustrates how the students distinguish between scientific and non-scientific questions and make value-judgements about relevance. The results contribute to an understanding of what the capability to engage in scientific inquiry as participation in collective epistemic work in an upper-secondary school science classroom might entail. The themes are related to the establishing of a specific scientific epistemic object. The results are discussed in relation to previous research in science education and the development of resources for teaching inquiry framing capabilities of inquiry as generic.
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