No description available.

No description available.

As China has celebrated its economic boom over the past decades, scientific research within the R&D sector of industry has become an active arena for Science and Technology Studies (STS) in understanding how science contributes to social change in China. Two themes are central in this sociological work: the study of secular change in China, in particular, change in its biotech industries exemplified by work in the BGI (formerly known as Beijing Genomics Institute); the investigation of interdisciplinarity in that context. This research sheds new light on explanatory practice in interdisciplinary research (IDR) strategy as patterns of interaction in the social process of scientific knowledge production, and its contribution also includes bridging the sociology of scientific knowledge production and research policy studies. In this thesis, I examine a number of topics at three interrelated levels of analysis. First, it explores the theoretical development of the academic discipline and the notion of interdisciplinarity, with a focus on the balance of normative and descriptive approaches in understanding their social functionality as embodied by what I name as Paradiscipline (the initial stage of IDR project). The second level investigates closely how IDR patterns emerge and evolve in the sequencing-based industrial R&D practice in the case of the BGI. Social, cultural, and institutional factors directing and conditioning collective actions by status groups within interaction network are carefully weighed against the context that scientific expertise speak to power in China's social setting. The last level is dedicated to yield more pervasive implications including the organizational structure of interaction and modelling of scientific research, via comparative analysis of traditional S&T management and governing 'Big Science'. It further addresses the issues around on-site governance of China's biotechnology industry R&D, at both management practice and policy making levels, on the basis of social embedment.

Background: There has been tremendous progress in the use of genomics1 in biomedical research and medical care since the launch of the Human Genome Project in 1990. However, it has also introduced new ethical challenges regarding the feedback of findings generated in genomic sequencing. While some would argue in support of the return of individual findings generated from genomics research, participants' preferences regarding which findings should be fed back differs. Most literature discusses feedback of findings in high income countries and very few address this issue in lower and middle-income countries (LMICs). As a result, it remains unclear whether and how individual findings from genomic studies in Africa should be fed back, who should provide these results and when. Methods: In order to contribute to addressing this gap, an empirical study was conducted to explore expectations and preferences for feedback of individual genetic findings in an HIV-TB genomics research project in Botswana. A qualitative study methodology involving deliberative focus group discussions (dFGDs) and in-depth interviews (IDIs) was used. Participants for this study were adolescents involved in an HIV-TB genomics study being conducted at the Botswana-Baylor Children's Clinical Centre of Excellence (BBCCCE). Parents and caregivers of children enrolled in that same genomic study were also enrolled in this study. A total of 93 participants (44 adolescents and 49 parents and caregivers) were enrolled in 12 dFGDs (6 groups of adolescents and 6 groups of parents and caregivers). Each group of participants met twice within a week, resulting in a total of 24 dFGD meetings. Participants of the dFGDs and in-depth interviews were selected purposively. Additionally, indepth interviews were conducted with 12 dFGD participants (6 adolescents and 6 parents or caregivers). The dFGDs and IDIs were conducted in Setswana, audio-recorded, transcribed and translated into English. Data were imported into NVivo 12 and analysed using the framework approach for qualitative data analysis. Results: The study findings revealed that participants' desire to receive individual genetic results is underpinned by their cultural values, mainly solidarity and reciprocity. Participants viewed research participation as a mutual relationship and considered the return of research results to be one way of reciprocating their efforts. This seems to be underpinned by the principle of Ubuntu which advocates for solidarity and reciprocity within communities. Participants noted that when reciprocity obligations are respected, participants feel valued and expressed that not respecting reciprocity expectations could undermine participants' trust and participation in future studies. Almost all participants wanted to receive individual genetic results. While parents and caregivers wanted to receive individual genetic results regardless of their severity, preventability or actionability, adolescents were reluctant to receive results for genetic conditions that are severe and non-preventable, especially if they are also unactionable. Participants advanced different reasons for feedback of results including for awareness, improving lifestyle, accepting one's' situation, and preparing for the future. The findings also reveal the importance of taking into account participants' context, relations and empowerment when making decisions about whether and which results ought to be fed back. When asked about practical considerations for feedback of results, both adolescents and parents expressed that they would prefer to receive individual genetic results in person, with adolescents preferring researchers to provide feedback, while parents preferred feedback from doctors associated with the study. Adolescents and parents both expressed that feedback should be supported by counselling, but they differed on the timing of feedback. Most participants shared that they would like to be informed about the possibility of discovering individual genetic results during the consent process and that consent be obtained for feedback during the enrolment process. They further expressed that in cases where prior consent to feedback was not obtained, then participants should be re-contacted where lifesaving genetic information is discovered. Participants emphasized the need for researchers to ensure that participants' decisions regarding feedback of results are well-informed. Autonomy, transparency, and communication were identified as key values to uphold during the consent process. Conclusion: In conclusion, expectations of solidarity and reciprocity could translate into an obligation to feedback selected individual genetic results in African genomics research. Decisions on practicalities for feedback of results should take into account participants' context and considerations of participants' preferences. For example, in settings like BBCCCE it might be feasible for the study team to relay participants' results to treating doctors in the same centre, while also organising counselling services if necessary. However, in cases where a study is done in a public facility with limited resources, that could be difficult to implement. Consequently, researchers may have to take up the responsibility of feeding back individual results as well as providing genetic counselling in such settings. To make these decisions, researchers should engage with relevant stakeholders including policymakers and local Institutional Review Boards (IRBs) so as to make informed decisions regarding the feasibility and acceptability of their approach to feedback of results. Obtaining participants' consent for feedback of results is important to ensure that their rights and wellbeing are protected in research. This is critical in building trust relationships between participants and researchers. Lastly, although this study is focused in Botswana, these findings could also be generalised to similar contexts in Africa and provide an authoritative voice to H3Africa to be able to mandate projects with potential to generate individual genetic results to make provisions to feedback these results to study participants.

Indiana University-Purdue University Indianapolis (IUPUI) / RNA-binding proteins (RBPs) are vital post-transcriptional regulatory molecules in transcriptome of mammalian species. It necessitates studying their expression dynamics to extract how post-transcriptional networks work in various mammalian tissues. RNA binding proteins (RBPs) play important roles in controlling the post-transcriptional fate of RNA molecules, yet their evolutionary dynamics remains largely unknown. As expression profiles of genes encoding for RBPs can yield insights about their evolutionary trajectories on the post-transcriptional regulatory networks across species, we performed a comparative analyses of RBP expression profiles across 8 tissues (brain, cerebellum, heart, lung, liver, lung, skeletal muscle, testis) in 11 mammals (human, chimpanzee, gorilla, orangutan, macaque, rat, mouse, platypus, opossum, cow) and chicken & frog (evolutionary outgroups). Noticeably, orthologous gene expression profiles suggest a significantly higher expression level for RBPs than their non-RBP gene counterparts, which include other protein-coding and non-coding genes, across all the mammalian tissues studied here. This trend is significant irrespective of the tissue and species being compared, though RBP gene expression distribution patterns were found to be generally diverse in nature. Our analysis also shows that RBPs are expressed at a significantly lower level in human and mouse tissues compared to their expression levels in equivalent tissues in other mammals: chimpanzee, orangutan, rat, etc., which are all likely exposed to diverse natural habitats and ecological settings compared to more stable ecological environment humans and mice might have been exposed, thus reducing the need for complex and extensive post-transcriptional control. Further analysis of the similarity of orthologous RBP expression profiles between all pairs of tissue-mammal combinations clearly showed the grouping of RBP expression profiles across tissues in a given mammal, in contrast to the clustering of expression profiles for non-RBPs, which frequently grouped equivalent tissues across diverse mammalian species together, suggesting a significant evolution of RBPs expression after speciation events. Calculation of species specificity indices (SSIs) for RBPs across various tissues, to identify those that exhibited restricted expression to few mammals, revealed that about 30% of the RBPs are species-specific in at least one tissue studied here, with lung, liver, kidney & testis exhibiting a significantly higher proportion of species specifically expressed RBPs. We conducted a differential expression analysis of RBPs in human, mouse and chicken tissues to study the evolution of expression levels in recently evolved species (i.e., humans and mice) than evolutionarily-distant species (i.e., chickens). We identified more than 50% of the orthologous RBPs to be differentially expressed in at least one tissue, compared between human and mouse, but not so between human and an outgroup chicken, in which RBP expression levels are relatively conserved. Among the studied tissues (brain, liver and kidney) showed a higher fraction of differentially expressed RBPs, which may suggest hyper- regulatory activities by RBPs in these tissues with species evolution. Overall, this study forms a foundation for understanding the evolution of expression levels of RBPs in mammals, facilitating a snapshot of the wiring patterns of post-transcriptional regulatory networks in mammalian genomes. In our second study, we focused on elucidating novel features of post-transcriptional regulatory molecules called as circRNA from LongPolyA RNA-sequence data. The debate over presence of nonlinear exon splicing such as exon-shuffling or formation of circularized forms has finally come to an end as numerous repertoires have shown of their occurrence and presence through transcriptomic analyses. It is evident from previous studies that along with consensus-site splicing non-consensus site splicing is robustly occurring in the cell. Also, in spite of applying different high-throughput approaches (both computational and experimental) to determine their abundance, the signal is consistent and strongly conforming the plausible circularization mechanisms. Earlier studies hypothesized and hence focused on the ribo-minus non-polyA RNA-sequence data to identify circular RNA structures in cell and compared their abundance levels with their linear counterparts. Thus far, the studies show their conserved nature across tissues and species also that they are not translated and preferentially are without poly (A) tail, with one to five exons long. Much of this initial work has been performed using non-polyA sequencing thus probably underestimates the abundance of circular RNAs originating from long poly (A) RNA isoforms. Our hypothesis is if the circular RNA events are not the artifact of random events, but has a structured and defined mechanism for their formation, then there would not be biases on preferential selection / leaving of polyA tails, while forming the circularized isoforms. We have applied an existing computational pipeline from earlier studies by Memczack et. al., on ENCODE cell-lines long poly (A) RNA-sequence data. With the same pipeline, we achieve a significant number of circular RNA isoforms in the data, some of which are overlapping with known circular RNA isoforms from the literature. We identified an approach and worked upon to identify the precise structure of circular RNA, which is not plausible from the existing computational approaches. We aim to study their expression profiles in normal and cancer cell-lines, and see if there exists any pattern and functional significance based on their abundance levels in the cell.

This item contains the agenda, minutes, and attachments for the Faculty Senate meeting on this date. There may be additional materials from the meeting available at the Faculty Center.