단백질 합성효소(ARS)의 세포 조절 기작에 관한 가설 생성 연구

최재영 연세대학교 대학원 2021 국내석사

Conceptual biology is a new research trend in the field of biomedical science that seeks to gain new insights by collecting fragmented knowledge by reviewing the findings of biomedical fields accumulated in multiple databases and linking related concepts. The concept of conceptual biology has also been applied to modern drug developments, with the rapid development of text mining techniques to extract desired information from biomedical data, such as paper publications, systematically well managed. However, conceptual biology is still not the main methodology for biomedical and new drug development research. This is because there is a deep-rooted perception among researchers that hypotheses generated and proposed in an automated manner through biomedical text mining technology are less reliable than those made by conventional research methods. Therefore, prior to recklessly introducing new hypotheses and drug targets under the banner of conceptual biology, it is necessary to show that the research results obtained through the existing experimental-oriented research methods can be derived equally by computerized text mining techniques. Therefore, in this work, we first demonstrate how reliable the connections between entities extracted from unstructured text data are through comparisons with existing research cases, and then apply the methodology to actual new drug target discovery to propose new hypotheses and materials to researchers. In this process, we used the theoretical framework of literature-based discovery (LBD) to bridge between conceptual biology and the field of library and information science, and used an enzyme called aminoacyl-tRNA synthetase (ARS), which has recently been spotlighted as a criterion for finding drug target proteins, as a key research material. To implement the above intentions and configurations in practice, the research procedure was also conducted in two major steps. First, in the first part, we summarized the existing research results related to ARS and expressed them in the form of a series of paths, and then, examined whether they could be reproduced in the same way through the currently used text mining technique. In this process, research papers related to the three pairs of ARS and amino acids (LARS1/leucine, QARS1/glutamine, MARS1/methionine) were used as the standard. And by comparing the results when the literature related only to the contents of LARS1/leucine, QARS1/glutamine, and MARS1/methionine were used separately with when all the literatures were combined, we wanted to visually identify the benefits of increasing the size of the literature group to be analyzed. As a result of the experiments, it was confirmed that most of the contents of the standard papers were reproduced through text mining techniques, demonstrating that this research method is fully utilizable unlike researchers' stereotypes. In particular, it is shown that the papers are better represented when using the entire data compared to utilizing only the literature groups directly related to the hypothesis we want to generate, indicating that even if we aim to generate hypotheses in a particular ARS field, it is better to utilize the data around it. Also, throughout this process, we also coordinate and optimize the specifications of the methodology, including the type of named entity dictionary to be used, the stop words list to be included, and the categories of data to be analyzed, to lay the foundation for what will follow. Meanwhile, in the latter part of the study, we explored substances that mediated the interaction between ARS and amino acids, and proposed new features of ARS which have not yet been proven. Especially, ranking algorithm was applied to the derived paths, allowing researchers to preferentially review materials that are expected to be worth studying as targets for new drug development. To this end, a total of three ranking mechanisms were devised and utilized: using the centrality indicators of words, considering the frequency of relations, and applying the ratio of relation frequency. And, as a result, in case of the second method, utilizing the frequency of relations, the results of previous studies in the first half were found to be at the highest rank. In addition, the last one section of the latter part of the study was assigned to the contents of substituting our methodology to the field of WARS1/tryptophan, where all operating mechanisms were not fully elucidated, being added a new attempt to express in an explicit path what has not yet been directly identified. Through this, we reinforced the usefulness of our research methodology by reconfirming the contents suggested only as hypotheses through partial experiments and contexts. At the same time, we were also able to enjoy the effect of presenting other possible paths that could lead to the development of new drugs. Despite the existence of some limitations, such as limited use of relation classification models using deep learning and incompleteness of text subject to analysis solely on titles and abstracts, this work is significant in that it systematically proves that the methodology of conceptual biology can be used in drug target discovery on several grounds. Starting with this study, if conceptual biology is more commonly used for biomedical and drug development research, it is expected that various social and economic costs incurred in the related research process will be dramatically reduced. Conceptual biology는 여러 데이터베이스에 축적된 생물 의학 분야의 연구 결과물들을 개념 중심으로 검토하고 관련된 개념들을 서로 연결 지음으로써, 단편적으로 산재해 있는 지식들을 모아 새로운 통찰을 얻고자 하는 생물 의학 분야의 새로운 연구 조류이다. 이러한 conceptual biology의 개념은 현대의 신약 개발 과정에도 응용되고 있는데, 타 분야에 비해 논문 출판물과 같은 비정형 데이터가 체계적으로 잘 관리되고 있는 생물 의학의 분야적 특성과 더불어 이들 데이터로부터 원하는 정보를 추출 해낼 수 있는 텍스트 마이닝 기법이 빠르게 발전하고 있다는 점 또한 그 원인이 되고 있다. 하지만 여전히 conceptual biology는 생물 의학 및 신약 개발 연구에 있어 주된 방법론으로 자리하지는 못하고 있다. 이는 바이오 텍스트 마이닝 기술을 통해 자동화된 방식으로 생성되고 제안된 가설들이 기존의 연구 방식에 의한 그것들에 비해 덜 믿을만하다는 인식이 연구자들 사이에 뿌리 깊게 퍼져 있기 때문이다. 따라서 무작정 conceptual biology의 기치 아래 새로운 가설 및 약물 표적을 내놓기에 앞서, 기존의 실험 중심 연구 방식으로 얻어낸 연구 결과들을 컴퓨터를 활용한 텍스트 마이닝 기법을 통해서 역시 동일하게 도출해낼 수 있음을 보일 필요성이 있다. 따라서 본 연구에서는 텍스트 마이닝 기법을 통해 비정형 텍스트로부터 추출된 개체 간 연결 관계들이 얼마나 믿을만한 지를 기존의 연구 사례들과의 비교를 통해 먼저 입증한 후, 해당 방법론을 실질적인 신약 표적 발굴에 적용하여 새로운 가설 및 물질들을 관련 연구자들에게 제안하는 방식을 택했다. 이 과정에서 문헌 기반 발견법이라는 이론적 틀을 활용하여 conceptual biology와 문헌정보학 분야 간의 다리를 놓았으며, 최근 약물 표적 단백질을 찾아내기 위한 기준으로서 각광받고 있는 ARS (aminoacyl-tRNA synthetase)라는 효소를 핵심 연구 소재로 삼았다. 상기한 의도와 구성을 실제 구현하기 위해, 연구 절차 또한 크게 두 단계로 나뉘어 수행되었다. 먼저, 전반부에서는 ARS와 관련된 기존의 연구 결과들을 요약하여 일련의 경로 형태로 표현하고, 현재 사용하고 있는 텍스트 마이닝 기법을 통해 이들을 똑같이 재현해 낼 수 있는지를 살폈다. 이 과정에서 세 쌍의 ARS 및 아미노산 LARS1/leucine, QARS1/glutamine, MARS1/methionine 등과 관련된 세 부류의 연구 논문을 기준으로 하였으며, LARS1/leucine, QARS1/glutamine, MARS1/methionine 각각의 내용과만 관련된 문헌을 별도로 활용한 경우와 전체 문헌을 모두 합쳤을 시의 결과를 비교함으로써 분석 대상 문헌 집단의 크기를 늘리는 데에서 오는 이점을 가시적으로 확인하고자 하였다. 실험 결과, 기준이 되었던 논문의 내용들이 텍스트 마이닝 기법을 통해서도 대부분 재현되는 것이 확인되어, 연구자들의 고정 관념과는 달리 본 연구 방식이 충분히 활용할 만한 것임을 입증할 수 있었다. 특히, 생성하고자 하는 가설과 직접적으로 관련된 문헌 집단만을 활용하는 것에 비해 수집한 전체 데이터를 이용할 때에 논문의 내용이 보다 잘 재현되는 것으로 나타나, 특정 ARS 분야의 가설을 생성하는 것을 목표로 하더라도 그 주변부의 데이터까지 활용하는 것이 옳은 판단임을 알 수 있었다. 또한, 이러한 과정을 거치며 사용해야 할 개체명 사전의 종류, 불용어로 포함시킬 단어의 목록, 이용할 데이터의 범주 등 해당 방법론의 구체적인 사항들을 조정하고 최적화하여, 이어질 내용을 위한 기반을 마련하였다. 한편, 연구의 후반부에서는 ARS와 아미노산 간의 상호작용을 매개하는 물질들을 발굴하고, 이를 통해 아직까지 증명되지 않은 ARS의 새로운 기능들을 제안하는 내용을 다루었다. 특히, 도출된 경로 집단에 순위화 방법론을 적용하여, 신약 개발의 표적으로서 연구할 가치가 있을 것으로 예상되는 물질 및 이를 포함한 경로들을 우선적으로 검토할 수 있게끔 하였다. 이를 위해 단어의 중심성 지표를 활용하는 방법, 관계의 빈도를 이용하는 방식, 관계 빈도의 비율을 적용하는 방안 등 총 세 가지 순위화 기제를 고안하여 활용하였는데, 관계의 빈도를 활용했을 때에 전반부에서 이용되었던 종전의 연구 결과들이 가장 높은 순위에 위치함을 확인할 수 있었다. 또한, 후반부 연구의 마지막 한 절을 모든 작동 기제가 완전하게 규명되지 않은 WARS1/tryptophan 관련 분야에 본 연구의 방법론을 대입하는 내용에 할당하여, 아직 직접적으로 밝혀지지는 않았지만 지금까지의 연구를 통해 유추만 가능했던 내용을 명시적인 경로로 표현해 보는 새로운 시도를 덧붙였다. 이를 통해, 부분적인 실험과 정황을 통해서 가설로만 제안되었던 내용을 문헌 기반 발견법을 통해 다시 한번 확인함으로써 본 연구 방법론의 유용성을 강화함과 동시에, 신약 개발로 이어질 가능성이 있는 또 다른 경로들을 함께 제시하는 효과를 누릴 수 있었다. 본 연구는 딥러닝을 활용한 관계 분류 모델이 제한적으로만 활용되었다는 점, 분석 대상 텍스트가 제목 및 초록에 한정되어 있다는 점 등 몇몇 한계점이 존재함에도 불구하고, conceptual biology의 방법론이 신약 표적 물질 발굴에 실질적으로 이용될 수 있음을 여러 근거를 들어 체계적으로 증명했다는 점에서 큰 의의를 지닌다고 볼 수 있다. 본 연구를 기점으로 conceptual biology 방법론이 생물 의학 및 신약 개발 연구에 더욱 보편적으로 활용된다면, 관련 연구 과정상에 발생하는 각종 사회적·경제적 비용을 획기적으로 절감할 수 있을 것으로 기대한다.

합성생물학 유래 생물체(LMO)에 대한 국제법적 적용가능성 : 생물다양성협약 및 바이오안전성의정서를 중심으로

이선빈 중앙대학교 대학원 2022 국내석사

Synthetic biology is being discussed internationally in many fields such as science and technology, society, and the environment. Synthetic biology, which creates new results based on large-scale genome information, can be advanced to solve human problems such as climate change, poverty, and hunger with infinite development potential. In contrast to the positive aspects, however, the potential impact must also be considered to ensure safety. Synthetic biology, a newly discussed issue, does not even have a defined definition yet, and the regulation is not clear. Therefore, as discussions on the regulation of synthetic biology are being actively conducted internationally, this study aimed to explore the possibility of regulating synthetic biology under international law. Regarding the possibility of regulation under general international law, synthetic biology does not violate the national liability law but the state's responsibility cannot be avoided if it violates other international obligations as a result of synthetic biology. In addition, considerable care must be taken to ensure that research and commercial applications of synthetic biology do not cause environmental damage to other countries, and an environmental impact assessment should be carried out if there is a possibility of serious adverse effects on the environment. Now, the Conference of the Parties is discussing the regulation of synthetic biology based on the precautionary principle under general international law. In addition, it is necessary to examine the possibility of regulation in the relevant international conventions. First, in accordance with the Agreement on the Application of Sanitary and Phytosanitary Measures(SPS), import restrictions on components, organisms, and products made with synthetic biology technology can be set but mainly focused on trade-related measures, which cannot be defined as related to synthetic biology technology. Second, the International Treaty on Plant Genetic Resources for Food and Agriculture (ITPGRFA) may relate to sharing benefits from accessing and commercializing genetic resources for synthetic biology processes. Third, suppose a new plant variety is produced through synthetic biology research. In that case, it may be subject to “breeder’s right,” according to the International Union for the Protection of New Varieties of Plants (UPOV). In particular, if synthetic biology technology develops, produces, and stocks microorganisms, other biological agents, and various toxins, it may be subject to the Biological Weapons Convention (BWC). Fifth, although the International Plant Protection Convention (IPPC) has guidelines for the standard application of genetically modified organisms, there are no guidelines for components and organisms resulting from synthetic biology technology. Lastly, if synthetic biology is an invention that complies with patentability standards, it can be guaranteed a patent under the WTO Trade-Related Intellectual Property Rights Agreement (TRIPs). Regulations under international conventions will vary depending on how the definition and scope of synthetic biology are defined. Synthetic biology is now being actively discussed in the Convention on Biological Diversity, the Nagoya Protocol, and the Cartagena Protocol. First, it acknowledged that synthetic biology is a cross-issue in the Convention on Biological Diversity, and admits that it is necessary to review the Cartagena Protocol and the Nagoya Protocol annexed to the Convention. Therefore, it is necessary to examine the applicability of synthetic biology under the Nagoya Protocol and to define whether the components, organisms, and products created in synthetic biology are “derivatives” as defined in the Nagoya Protocol. In particular, this paper has addressed in detail about relevance to LMOs and living organisms and modern biotechnology, risk assessment and management for synthetic biology, unintentional cross-border movement of synthetic biology organisms and emergency measures, and matters related to handling, transport, packaging, and identification of synthetic biology organisms which are described in the Cartagena Protocol. It is expected that the Convention on Biological Diversity and its Annex Protocols will continue to discuss synthetic biology in the future. Although it is unlikely, an international discussion comprehensively and coherently is required to minimize the potential impact that may appear on a large scale. Finally, enacting an appropriate domestic legislative procedure on synthetic biology would be necessary along with international discussions. 현재 국제적으로 합성생물학은 과학기술, 사회, 환경 등 많은 분야에서 논의가 되어지고 있다. 대규모 유전체 정보를 바탕으로 새로운 결과물을 만들어내는 합성생물학은 무한한 발전 가능성과 기후변화, 가난, 기아 등 인류 난제의 해결로 발전할 수 있다. 하지만 긍정적인 면에 반해 잠재적 영향도 생각을 해야 하며 안전성을 확보해야 한다. 합성생물학은 새롭게 논의되는 이슈로 아직 규정된 정의조차 없고 규제가 명확하지 않다. 이에 국제적으로 합성생물학 규제에 대한 논의가 활발하게 이루어지고 있으며 국제법상 합성생물학의 규제가능성에 대하여 알아보았다. 일반 국제법상 규제 가능성에 대하여 합성생물학이 국가책임법에 위반되지는 않지만 합성생물학의 결과물로 다른 국제적 의무를 위반하게 된다면 국가책임을 피할수 없을 것이다. 또한 합성생물학의 연구와 상업적 응용 분야가 타국가에게 환경적인 피해를 끼치지 않게 상당한 주의를 해야 하며 환경에 심각한 악영향을 초래할 가능성이 있다면 환경영향평가를 수행해야한다. 현재 당사국총회는 일반국제법상의 사전예방원칙을 바탕으로 합성생물학에 대한 규제논의를 진행하고 있다. 더불어 관련 국제 협약상 규율 가능성도 살펴볼 필요가 있다. 첫째, WTO 위생검역협정에 따라 합성생물학 기술로 만들어진 구성요소, 유기체 및 산물에 대한 수입 제한을 설정할 수 있지만 주로 무역에 관련 조치에 초점을 맞추었고 합성생물학 기술과 관련되었다고 정의할 수 없다. 둘째, 식량농업식물유전자원에 관한 국제조약(ITPGRFA)은 합성생물학 공정에 사용하기 위한 유전자 자원 접근 및 상업화로부터 발생하는 이익의 공유와 관련이 될 수 있다. 셋째, 합성생물학 연구로 새로운 식물 품종이 생산된다면 식물신품종보호에 관한 국제협약(UPOV)에 따라 “육성가 권리”에 해당 할수도 있다. 특히 합성생물학의 기술로 미생물 혹은 기타 생물학적 작용제, 여러 가지 독소를 개발, 생산, 비축한다면 생물무기금지협약(BWC)에 해당될 수 있다. 다섯째, 국제식물보호협약(IPPC)은 유전자변형생물체에 대해 표준 적용을 위한 지침이 만들어졌지만 합성생물학 기술로 인한 구성 요소 및 유기체에 대한 지침은 존재하지않는다. 마지막으로 합성생물학이 특허성 표준을 준수하는 발명이라면 WTO 무역관련 지적재산권협정(TRIPs)에 따라 특허를 이용할수 있게 된다. 국제 협약상 규율은 합성생물학의 정의와 범위가 어떻게 규정되느냐에 따라서 규제방법이 다양할 것이다. 현재 합성생물학은 생물다양성협약과 나고야의정서, 카르타헤나의정서에서 활발하게 논의되고 있다. 우선 생물다양성협약에서 합성생물학이 교차이슈임을 인정하고 협약 부속의정서인 카르타헤나의정서와 나고야의정서의 검토가 필요하다고 인정하였다. 이에 나고야의정서 조약상 합성생물학의 적용성을 살펴볼 필요가 있다. 합성생물학에서 생성된 구성요소, 유기체 및 산물이 나고야의정서에 정의된 “파생물”에 해당하는지 정의해야 할 필요가 있다. 특히 본 논문에는 카르타헤나의정서에는 LMO 및 생물체 그리고 현대바이오기술에 해당성, 합성생물학에 대한 위해성 평가 및 관리, 합성생물학 생물체의 비의도적 국가간 이동 및 비상조치, 합성생물학 생물체의 취급·운송·포장 및 식별에 관련된 사항을 자세히 서술하였다. 생물다양성협약과 부속의정서들은 앞으로 합성생물학에 대하여 꾸준한 논의가 진행될 것으로 예상된다. 가능성은 낮지만 거대한 규모로 나타날 수 있는 잠재적 영향을 최소화하는 전제로 포괄적이고 일관성있는 방식의 국제 논의가 필요하다. 마지막으로 국제 논의에 맞추어 합성생물학에 관한 적절한 국내 입법절차를 제정해야 할 필요가 있다. 目前,国际领域对合成生物学在科学技术、社会、环境等诸多领域都进行了讨论。以大量基因信息为依托并创造出新成果的合成生物学存在无限的发展可能性,并可解决气候变化、贫困、饥饿等人类难题。但是,考虑积极一面的同时,还要考虑潜在的影响以确保安全性。合成生物学是新讨论的话题,目前还没有规定的定义,限制也不明确。对此,国际上正在积极讨论合成生物学的限制问题,并找寻国际法层面上的合成生物学限制的可能性。 对于一般国际法上的限制可能性,合成生物学虽然不违反国家责任法,但是合成生物学的结果如果违反其他国际义务,将不可避免地承担国家责任。 另外,合成生物学的研究和商业应用领域要相当注意,以免给其他国家造成环境损失,如果有可能对环境造成严重负面影响,就要进行环境影响评价。 目前,当事国总会正在以一般国际法的事前预防原则为基础,对合成生物学进行限制讨论。 同时,有必要观察相关国际协议中的规律可能性。第一,根据WTO卫生检疫协定,虽然可以设定对合成生物学技术制造的构成要素、有机体及产物的进口方面进行限制,但将焦点放在贸易相关措施上,不能定义为与合成生物学技术有关。 第二,粮食农业植物遗传资源相关国际条约(ITPGRFA)可能与用于合成生物工程的遗传资源接近,与商业化产生的利益共享有关。第三,如果通过合成生物学研究生产出新的植物品种,根据《植物新品种保护国际公约》(UPOV),可以相当于是"培育的权利" 。特别是利用合成生物学技术对微生物、其他生物学作用剂、多种毒素进行开发、生产、储备,就相当于违反《生物武器禁止公约》(BWC)。 第五,《国际植物保护公约》(IPPC)虽然制定了转基因生物体适用标准的方针,但是不存在合成生物学技术引起的构成要素及有机体的方针。 最后,如果合成生物学是遵守专利性标准的发明,那么根据WTO《与贸易相关的知识产权协定》(TRIPs)可以使用专利。 根据国际协议的规律,如何规定合成生物学的定义和范围,规制方法将多种多样。《生物多样性公约》、《名古屋议定书》和《卡塔赫纳议定书》对合成生物学问题目前正在积极讨论。首先,在《生物多样性公约》中承认合成生物学是交叉焦点,《卡塔赫纳议定书》和《名古屋议定书》主张讨论是有必要的,公约附属议定书也对此表示认可。因此,有必要分析《名古屋议定书》条约对合成生物学的适用性。有必要对合成生物学中生成的构成要素、有机体及产物是否属于《名古屋议定书》定义的"衍生物" 进行定义。特别是本论文中《卡塔赫纳议定书》详细叙述了LMO、生物体以及现代生物技术的相关性、对合成生物学危害性的评价及管理、合成生物学生物体非意图的国家间移动及紧急措施、合成生物学生物体的处理、运输、包装及识别等相关事项。预计《生物多样性公约》和附属议定书今后将继续对合成生物学进行讨论。 虽然可能性很低,但有必要考虑巨大规模出现时潜在影响的处理方法,以此为前提,需要以全面一贯的方式进行国际讨论。 最后,有必要根据国际讨论制定适当的国内立法程序。

Towards a Scalable, Future-Proof Platform for Dynamical Modeling in Biology

Medley, J. Kyle University of Washington ProQuest Dissertations & 2019 해외박사(DDOD)

Mathematical models are used widely throughout the sciences, and often influence not only research, but our daily lives. For example, weather prediction is made possible by numerical weather models that have advanced steadily since computers became widely available in the1970's. The improvements in weather models have been so consistent that some researchers have coined a "Moore's law" for weather models. In its original formulation, Moore's law states that the number of transistors in an integrated circuit such as a CPU approximately doubles every year. The weather forecasting equivalent states that the accuracy of numerical weather models improves by ten percent every ten years. Systems biology models do not advance to a steady drumbeat as weather models do. It can hardly be claimed that a ten year period yields a ten percent universal improvement in systems biology. In fact, current systems biology models are in many ways more primitive than weather models.Systems biology models (especially detailed, mechanistically-accurate models) are underutilized in synthetic biology and are almost completely absent from the clinic. This is unfortunate, because systems biology models have the potential to혻aid in drug discovery,혻cancer treatment,혻disease biology, and혻production of biofuels.Why are systems biology models so underutilized, despite considerable advances in computing power and experimental data? There are at least three major factors: difficulty in model reuse, lack of scalability, and lack of technological advances for simulation. Specifically, these three factors are due to the following problems:1. Perhaps more so than any other field, models in systems biology need to be reusable and reproducible. Due to the complexity of biology, no single research team can specialize in every subsystem of the cell. Therefore, models of cellular subsystems must be developed, validated, and analyzed by different research teams, and combined into a single, larger model of the cell. This can only happen if researchers use uniform standards to store their work, and provide a means for others to reuse and incorporate their models.2. As the size of a model increases, so do the resources required to simulate it. This is not simply an issue of convenience, since tting a model requires simulating it many times. The strain on computational resources has caused many groups to use simpler "constraint-based" modeling approaches. However, this approach trades detail for performance. Continued advancement of systems biology requires the development of mechanistically accurate kinetic models, which is currently hampered by scalability constraints.3. Finally, despite decades of innovation in computer simulation, kinetic models are still commonly simulated using 40-year old solvers such as LSODA. It is natural to ask whether advancements in computer technology could be used to provide a better approach to simulating models. Indeed, this thesis considers state-of-the-art specialized silicon hardware specifically designed to simulate kinetic models.This thesis seeks to address these factors through technological innovations which enable the construction of larger, more accurate, and more robust models. This is accomplished through providing better solutions for encoding and reusing models, providing a scalable solution for optimizing large, challenging kinetic models, and providing a way to simulate models on special-purpose hardware. Taken together, these foundational advances in modeling technology provide a pathway toward building larger, more complex, and more accurate models.

Laws, causes, and kinds: Toward a solution to the biology problem

Hamilton, Andrew University of California, San Diego 2005 해외박사(DDOD)

Philosophers of science have long focused on physics in formulating answers to philosophical questions. When asking about realism, explanation, or theory change, for example, physics has been the central---sometimes the only---science from which cases and examples are drawn. Philosophers of biology have not much tried to correct this narrowness of attention, turning their energies instead to questions about what species are, what the unit of selection is, or how explanation works in biology. This dissertation attempts to build a bridge between philosophy of science and philosophy of biology by asking whether the divisions between the two sciences are as deep as many have argued. My analysis finds its impetus in law-based approaches to science, and the project centers on dissolving what I call the biology problem for philosophy of science. Some argue that there are differences between the biological sciences and the physical ones that stem from the complexity or contingency of evolved systems. Proponents of this view contend that complexity, contingency, or other features of biological systems stand in the way of laws of biology. From this arises the further question of how many philosophies there ought to be. If evolved systems are anomic, do we need a separate accounting of them?. Here I argue by way of careful analyses of complexity and contingency in biology that the differences between physics and biology, at least with respect to laws, are largely artificial. The central move is to deny the characteristic complexity and contingency of biological systems by pointing to complexity and contingency in central parts of physics. I also gesture at an answer to the second question, arguing that dissolving the biology problem also dissolves the motivation behind asking how many philosophies of science there are. This dissertation also contains a pair of case studies---one on selection on higher taxa and one on kinds at the foundations of ecology and conservation biology. These cases take as their touchstone the discussion of explanation that emerges from my dissolution of the biology problem. That discussion argues for local explanations in which laws do not play a central role, and the case studies are examples of such explanations.

Promoting Indonesian Pre-Service and In-Service Biology Teachers’ Perceptions and Teaching Practices on Socioscientific Issues (SSI)

파이살 서울대학교 대학원 2021 국내박사

In Indonesia, scientific literacy has been a major goal of the school science curriculum. To achieve this goal, however, teachers need appropriate teaching resources. Previous studies in science education have documented that instruction based on socioscientific issues (SSI) is a pedagogical approach that has the potential to improve students’ scientific literacy competencies. However, its effective implementation in the classroom requires science teachers to have adequate pedagogical knowledge and skills. In this study, I designed and implemented a science methods course to equip pre- and in-service biology teachers with the theoretical framework and practical implementation of SSI-based instruction. Specifically, this study is divided into three parts: exploring in-service biology teachers’ perceptions about SSI, examining pre- and in-service biology teachers’ perceptions of SSI-based instruction after participating in an SSI teaching-oriented course, and exploring pre- and in-service biology teachers’ SSI-based teaching practices during the course. To explore biology teachers' perceptions about SSI, I surveyed 123 in-service biology teachers using a questionnaire. I also used a survey to pilot the SSI-based biology instruction (BI) questionnaire. The results of the analysis indicated that the majority of the SSI topics identified by the teachers involved biology-associated content in the curriculum, such as environmental pollution, global warming, and biotechnology. Teachers also used general methods such as discussion and cooperative learning to teach about these topics. Teachers also recognized environmental issues as important and interesting topics for implementing SSI lessons. The analysis of the SSI-BI questionnaire suggested that the 21 items could be divided into four scales: (1) core aspects of SSI-based instruction, (2) challenges in implementation, (3) pedagogical knowledge, and (4) attitudes and beliefs about SSI-based instruction. Building from these findings, I discuss how the topics the teachers selected reflected the characteristics of SSI and how the teaching and learning methods aligned with the framework of SSI-based instruction. I also explore the importance of each SSI-BI questionnaire scale for the successful implementation of SSI-based instruction. In the second part of this study, I engaged 45 pre- and in-service biology teachers in 8 weeks of an SSI teaching-oriented course. During the course, the teachers discussed the theoretical framework of scientific literacy, SSI and its teaching, and biology competencies in the Indonesian national curriculum. They also worked collaboratively in planning and implementing SSI teaching. Using data collected from the SSI-BI questionnaire (pre- and post-survey), interviews, and course assignments, I explored how the teachers’ engagement in the course had an impact on their perceptions and attitudes about SSI-based instruction. The results demonstrated that the course significantly affects the teachers’ perceptions of their pedagogical knowledge and attitudes about SSI-based instruction. They also recognized some core aspects of SSI-based instruction. However, teachers still considered factors such as curriculum requirements, teachers’ competency, and students’ characteristics as challenges for the implementation of SSI teaching in school. In addition, teachers expressed concerns about their capacity in designing SSI lessons and managing the SSI discussion activities. The third part of the study focuses on SSI-based teaching practices. Six teachers from two classes of the course implemented their SSI lesson plans in science methods classrooms. Each class implemented three different SSI lessons designed for the senior secondary school classroom (Grades 10-12). The SSI observation protocol (OP) was used as an analytical framework to examine the six videos of the lesson implementations. The SSI-OP consists of five dimensions: the focus of instruction, teaching moves, the role of the teacher, the role of the students, and the classroom environment. To evaluate biology teachers’ reflections about their teaching, six videos of post-teaching reflections were analyzed. The result from the video analysis corroborated the data from the classroom observation and teaching materials. The quantitative analysis shows that the classroom environment category had the highest standardized score, while the teaching moves category was the lowest. Results from the qualitative analysis indicate that most activities suggested in the five dimensions of the SSI-OP were implemented. However, there were some inconsistencies between the lesson plan and the actual teaching. The teachers also acknowledged that their teaching and the classroom situation may have been more challenging when they implemented the lesson in the real school context. Overall, this study indicates the potential of an SSI teaching-oriented course to improve pre- and in-service biology teachers’ perceptions of their pedagogical knowledge and attitudes about SSI-based instruction. This study also provides important evidence for how teachers practice SSI-based instruction and reflect on their teaching in the context of a science methods course. The findings of this study can lead science teacher educators and researchers to make more informed decisions regarding the content and activity of a science methods course to help pre- and in-service biology teachers improve their knowledge and skills in teaching SSI. 인도네시아에서는 과학 문해력이 과학과 교육과정의 주요 목표이다. 이 목표를 성취하기 위해 적절한 교육자료가 필요하다. 과학 관련 사회 쟁점(SSI) 교육은 학생들의 과학 문해력을 향상시킬 수 있는 잠재력을 가진 교육학적 접근법이라는 것에 대한 선행 연구들이 있다. 하지만 교실에서 효과적인 구현을 위해서는 과학 교사가 적절한 교육 지식과 기술이 있어야 한다. 본 연구에서는 생명과학 예비교사와 현직교사에게 SSI 기반 교육의 이론적 프레임 워크와 실제 구현을 제공하기 위해 ‘Science Methods Course’을 설계하고 구현했다. 구체적으로 본 연구는 SSI에 대한 현직 생명과학 교사의 인식 탐색, ‘Science Methods Course’에 참여한 후 SSI 수업에 대한 예비교사와 현직교사의 인식 검토, 예비교사와 현직교사의 SSI 수업 실행 조사 이렇게 세 부분으로 나뉜다. 이 연구의 첫 번째 부분에서는 SSI에 대한 생명과학 교사의 인식을 탐색하기 위해 설문지를 사용하여 123명의 생명과학 현직교사를 대상으로 설문 조사를 실시했다. 또한 SSI 기반 생명과학 수업(BI) 설문지를 시험하기 위해 설문 조사를 하였다. 분석 결과, 교사들이 생각한 SSI 주제의 대부분은 환경 오염, 지구 온난화 및 생명 공학과 같은 교육 과정의 생물학 내용과 관련이 있었다. 또한 교사들은 토론과 협력 학습과 같은 일반적인 방법으로 이러한 주제에 대해 가르쳤다. 교사들은 SSI 수업에서 환경 문제에 대한 주제가 중요하며 흥미롭다고 인식했다. SSI-BI 설문지 분석에 따르면 21개 항목은 (1)SSI 기반 수업의 핵심 측면, (2)실행의 과제, (3)교육학적 지식, (4)SSI 기반 수업에 대한 태도와 신념의 네 가지 척도로 나눌 수 있다. 이러한 연구 결과를 바탕으로 교사들이 선택한 주제가 SSI의 특성을 어떻게 반영했는지, 교수-학습 방법이 SSI 기반 수업의 프레임워크와 어떻게 일치하는지 논의하고자 한다. 또한 SSI 기반 수업을 성공적으로 구현하기 위해 각 SSI-BI 설문지 척도의 중요성을 탐색하고자 한다. 이 연구의 두 번째 부분에서는 ‘SSI teaching-oriented Course’ 8주 동안 45명의 생명과학 예비교사와 현직교사가 참여하였다. 이 과정에서 교사들은 인도네시아 국가 교육과정에서 과학적 문해력, SSI 및 교육, 생물학 역량의 이론적 프레임워크에 대해 논의하였다. 또한 교사들은 SSI 수업을 계획하고 실행하는 것에도 참여하였다. SSI-BI 설문지(사전 및 사후 설문 조사), 인터뷰, 과제에서 수집한 데이터를 사용하여 교사의 ‘SSI teaching-oriented Course’ 참여가 SSI 기반 수업에 대한 인식과 태도에 어떤 영향을 미치는지 조사했다. 결과적으로 이 과정이 SSI 기반 수업에 대한 교육적 지식과 태도에 대한 교사의 인식에 상당한 영향을 미치는 것으로 나타났다. 또한 교사들은 SSI 기반 수업의 몇 가지 핵심 측면을 인식했다. 그러나 교사들은 여전히 ​​교육과정 요건, 교사의 능력, 학생의 특성과 같은 요소들이 학교에서 SSI 수업을 실행하기 위한 과제라고 하였다. 또한 교사들은 SSI의 논란이 되는 측면을 식별하는 방법을 결정하고, 고차원적 사고 연습의 교육 목표를 공식화하고, SSI를 국가 교육과정의 구성 요소와 일치시키고, SSI 교육을 위한 적절한 수업을 설계하는 것을 어려워하였다. 연구의 세 번째 부분은 SSI 기반 수업 실행에 중점을 두었다. ‘Science Methods Course’ 두 개의 반에서 6명의 교사가 SSI 수업 계획을 시행했다. 각 반에서 고등학교 수업(10-12 학년)을 위해 고안된 세 가지 SSI 수업을 실행하였다. SSI 관찰 프로토콜(OP)은 수업 실행에 대한 6개의 비디오를 검토하기 위한 분석 프레임워크로 사용되었다. SSI-OP는 5가지 관점으로 구성된다: 수업의 초점, 수업의 흐름, 교사의 역할, 학생의 역할, 교실 환경. 수업에 대한 생명과학 교사의 성찰을 평가하기 위해 수업 후 6개의 성찰 비디오를 분석하였다. 비디오 분석 결과는 수업 관찰 및 교육 자료의 데이터를 확증했다. 양적분석에 따르면 교실 환경 범주가 표준화 점수에서 가장 높았고 수업의 흐름 범주가 가장 낮았다. 질적분석의 결과에서는 SSI-OP의 5가지 관점에서 제안된 대부분의 활동이 구현되었다. 그러나 수업 계획과 실제 수업 사이에 약간의 불일치가 있었다. 또한 교사들은 실제 학교 맥락에서 수업을 시행했을 때 교사의 교수법과 교실 상황이 더 어려울 수 있다고 하였다. 전반적으로 본 연구는 SSI 기반 수업에 대한 교육적 지식과 태도에 대한 생명과학 예비교사와 현직교사의 인식을 향상시키는 ‘SSI teaching-oriented Course’의 잠재력을 보여준다. 본 연구는 교사가 어떻게 SSI 기반 수업을 실행하고 ‘Science Methods Course’ 상황에서 교사의 교수법을 반영하는지에 대한 중요한 증거를 제공한다. 본 연구의 결과는 과학 교사 교육자와 연구자가 SSI 교육에 대한 생명과학 예비교사와 현직교사들의 지식과 기술을 향상시키는 데 도움이 되는 ‘Science Methods Course’의 내용과 활동에 대해서 좀 더 정보에 근거한 결정을 내리도록 이끌 수 있다.

중등학교 생물임용시험과 교육대학원 생물교육전공 교과과정의 관련성 분석

나기선 동국대학교 교육대학원 2008 국내석사

The purpose of this study is to analysis the relationship between Teachers' Appointment in Biology and Biology Education curriculums in the Graduate School of Education. The questions of Teachers' Appointment in biology are based on the biology education curriculums in the graduate school of education. Therefore the curriculums should consist of contents covering overall courses of study in secondary school, which would be fundamental for students to study in University or Graduate School. This study is about whether the questions in current Teachers' Appointment correspond well to requirements in the curriculums. In this study, I used three different approaches to address these questions as follow: First, I analyzed all the questions in biology Teachers' Appointment given last 5 years from 2003 to 2007. Second, I analyzed 6 biology education curriculums in the graduate schools of education which are represented each province. Third, I analyzed the relationship of the questions and curriculums and studied how to improve the teachers' appointment in the future. When the questions in biology were analyzed, the number of questions were not enough to cover all the contents suggested in the 7th Version of National Curriculum. In addition, the questions were not related to the modern environmental biology and biotechnology. In conclusion, graduate school of education must develop unique curriculum for biology major because it aims at training secondary school teachers and the curriculums should be standardized to be connected with secondary school of biology. Teachers have great responsibility which they must develop future leaders who lead our society. Therefore, it is crucial that we select right people for the position.

우리나라 현행 고등학교 생물교과서, BSCS 및 Nuffield Biology 의 생태단원에 대한 비교 연구

전태주 이화여자대학교 교육대학원 1986 국내석사

Philosophical Perspectives on Time in Biology

Valde, Katherine Grace ProQuest Dissertations & Theses Boston University 2019 해외박사(DDOD)

Although time is a central topic in philosophy, within the philosophy of science discussions of time in biology have largely been neglected. This dissertation argues for the philosophical importance of paying closer attention to the vastly different timescales at which biological phenomenon can be investigated and explained. The importance of timescales for four themes in philosophy of biology is examined: abstractions and manipulations of time in biological practice, metaphysical debates between the mechanistic and process ontology frameworks, the problem of synchronizing molecular clocks and fossil clocks, and reductionism in biology. This dissertation provides the first sustained philosophical examination of the role of time in biology. The first chapter explores how researchers manage the complexities of multiple timescales by abstracting from time physically, procedurally, mathematically, and conceptually. Understanding how researchers abstract from time in their investigations is important for determining what phenomena might be obscured by such practices. Chapter two turns to the debate in philosophy of biology between traditional mechanistic accounts and the new process ontology. While process ontology is an advance, insofar as it has the potential to bring temporal issues to the fore, it is better understood as an epistemological—not metaphysical—framework. A careful consideration of timescales highlights how different metaphysical frameworks can be more epistemologically appropriate in different contexts.The third chapter examines how molecular and fossil clocks are used to measure time in biology. In both cases, researchers use phenomena occurring at one timescale (e.g. DNA mutations) to measure durations across another scale (e.g., the evolutionary occurrence of a last common ancestor). Attempts to synchronize these clocks for key biological events in the deep past pose interesting methodological problems—and suggest new solutions—for how to deal with discordant and interdependent lines of evidence. The final chapter considers the consequences of this analysis of time in biology for debates about reductionism. Reductionism has focused almost exclusively on spatial scales. This chapter shows how a consideration of temporal scales transforms philosophical debates about reductionism in biology and poses new challenges. This dissertation demonstrates the fertility of extending the philosophy of time into the philosophy of biology.

The practice of theorizing in computational biology: Function, information, and mechanism

Sterner, Beckett W The University of Chicago 2012 해외박사(DDOD)

Biologists know more about the parts of organisms than ever before: they know the sequences of billions of nucleotides in thousands of genomes, and they've measured the concentrations of untold proteins across thousands of organisms. The research program collecting and analyzing this molecular data is called high-throughput biology. Yet what to do with all this new data poses a serious problem with ramifications for biological theorizing and our understanding of life. Physics has traditionally offered the dominant ideal for biological theory, but many biologists are now arguing that engineering and information science offer a better analogy. Similarly, the classic twentieth century division between genotype and phenotype, along with inheritance and development, is facing fundamental revision in light of new results from high-throughput biology. Settling these issues over the coming decades will require basic changes in the way biology works as a science. Particularly problematic is how the integrative, inter-disciplinary character of high-throughput biology makes it difficult to establish clear standards for evaluating contributions and progress. I offer a way of articulating and evaluating these standards in terms of normative content in the structure of scientists' research problems. Problem structures express entrenched commitments in research programs, and they are an analytic tool for studying the value of heuristics in the dynamic process of research. My dissertation focuses in particular on the problem structures governing theorizing in computational biology, a subfield of high-throughput biology. Computational modeling provides an attractive way of coping with the deluge of molecular data. Many biologists now represent cells as vast mathematical networks of molecules, for example, or they compare genomes by aligning them like two versions of a symbolic text. Integrating computational models into existing methods has been disruptive and contentious, however. Biologists continue to struggle with knowing when it has been done right and whether it was worthwhile. I investigate the epistemic conditions on the value of computational modeling in terms of the commitments biologists must make to warrant its application as relevant. These commitments include ontological theories that govern what biological phenomena various computational models can legitimately represent, along with epistemic theories about when these computational models can generate mechanistic explanations or predictions. I argue that a theory of biological information is central to the relevance of computational biology. Also, I argue that we can only understand the fruitfulness of computational biology by first recognizing the inferential interdependence of knowledge about functions and mechanisms. I articulate this interdependence via the temporal iterativity of various modeling heuristics in the course of the research process. These elements behind modeling are visible in what I call the normal form of research problems in computational biology, borrowing Culp and Kitcher's term (1989). They offer a powerful basis for judging the results of high-throughput biology. Articulating the meaning of theorizing in terms of its normative content for scientists' actions opens a new way of understanding the relation of mathematics and logic to the special sciences. My dissertation is thus connected with broader movements in philosophy of language, and I develop my argument in dialogue with work by Robert Brandom, Ruth Millikan, Mark Wilson, and the classical pragmatism of John Dewey. The pivotal question is the relation between the meaning of language, its formal structure, and its subject matter or material content. Theorizing in high-throughput biology is an interesting case precisely because its methodological standards are undergoing rapid development and the syntax and semantics of its theories are being contested. Hence I claim that Dewey's notion of warranted assertibility is the right way to conceive of the relations between steps in the process of theorizing.

Nuffield Advanced Science Biology에 대한 분석적 연구

김성미 이화여자대학교 교육대학원 1986 국내석사