MID is a course for molecular biologists on the implementation of molecular techniques and more specifically the use of molecular data in tropical low-resource settings. In the MID, molecular techniques and data are discussed in the context of clinical and epidemiological field studies on infectious diseases.
Pathogen identity, dynamics, and transmission often form an integral part of such studies. These phenomena can be documented using DNA and RNA techniques. Despite rapid advancements in molecular methods, their implementation in low-resource environments often remains cumbersome due to logistic, financial, and human resource constraints. MID focusses on the selection and analysis of appropriate assays and their implementation in a particular research setting.
Course participants work in small groups to develop their own project proposal and implementation plan.
At the end of the course the student should be able to:
- select the appropriate molecular methods for detection or characterization of an aetiological agent, in order to study its dynamics in a clinical or epidemiological research context, and given the restrictions in terms of infrastructure, logistics, personnel, and budget
- plan molecular data collection and analysis in a resource-limited context, while ensuring sufficient sample size for obtaining statistically meaningful results
- present the research proposal orally and in writing to fellow-students, course faculty, and a broader scientific community, including clear argumentation of relevance and feasibility
- infer research conclusions given the limitations of the proposed methods and sample size
- work in a team to develop and to peer-review a research proposal
The course is taught in English and offered in a blended format:
- E-learning: students receive an introduction on basic concepts and skills, in order to level all participants with relation to background knowledge and software proficiency before the face-to-face part.
- Face-to-face: students are coached to develop and present a study protocol for using molecular data in support of a clinical or epidemiological study in a low-resource setting.
- Pathogen models: HIV, Ebola, Mycobacterium, Salmonella, Plasmodium, Schistosoma, Leishmania, Trypanosoma
- Review papers: SOP writing for resource-limited settings, basic methods of phylogeny
- Molecular methods: fragment-based methods, DNA sequencing, nucleic acid isolation, PCR
- Software: MEGA, R, BLAST, Structure, Splitstree, spreadsheet
- Project assignment: develop, present, and peer evaluate a proposal in a multi-disciplinary team
- Study context: epidemiology, clinical studies
- Phylodynamics: bacteria, viruses
- Population dynamics: protozoa
- Molecular diagnostics: bacteria, viruses, protozoa
- Study preparation: ethics, Good Laboratory Practice (GLP), logistics
- Molecular data handling: protocol writing, data collection tools, database tools, quality control
Teaching and learning methods
In this part the student is offered a combination of online tutorials, manuals, videos and review papers to acquire the necessary background knowledge. The student studies the provided material and answers a short assessment for each individual topic. For the software proficiency, the student installs each freeware package on the laptop he will bring to Antwerp, and familiarizes himself with a given list of functionalities. The student uploads software-generated output to the online learning platform Moodle for evaluation.
The face-to-face part is built around a central assignment that is developed in groups of 2 to 4 students. Each group submits a written project proposal in a pre-defined template, and presents the project orally to fellow-students, faculty, and invited ITM scientists at the end of the course. During the course, students integrate the acquired knowledge into their project. The proposal contains several chapters, each related to a particular course session. The learning process is as follows:
- At the start of the course, students and course faculty select appropriate topics, and form the groups. Each student can suggest a project topic that fits with the course scope and his own interest. An appropriate topic studies a pathogen aspect related to the clinic or epidemiology of an infectious disease in a specific low-resource setting, using molecular data. These molecular data relate to the use of DNA or RNA to characterize or detect pathogens. Serological methods are not covered by the course. Students form small groups to develop each project, taking into account students’ background and interest. Examples of suited (hypothetical) topics are:
- Between 2014 and 2016, the number of sepsis patients infected by bacteria that show extended-spectrum beta-lactamase (ESBL) production increased in Loja province, Ecuador. Different classes of genes can cause this resistance phenotype. What is the prevalence of the different ESBL-genes per bacterial species within this region?
- Early 2017, an outbreak of visceral leishmaniasis has been discovered in elevated slopes (altitude above 500 m) in western Nepal. In support of studying the transmission cycle, which potential reservoirs and vectors are found infected with the parasite, is the same type of parasite present in different host species, and is the same parasite found in the Terai lowlands?
- In Burkina Faso, a clinical study compares the efficacy of chloroquine with artemether-lumefantrine in a two-armed trial. The study is conducted in five villages for each arm, in the Nanoro region. When a patient is diagnosed with malaria after treatment, it is important to recognize a new infection from recrudescence. Does the number of new infections versus recrudescences differ between the two arms?
- During the interactive lectures in week 2, students gradually integrate the acquired knowledge into their proposal. They discuss with faculty and fellow students.
- In the third course week, students decide which methods to use in their project, based on available public domain information in literature and databases. The students discuss the selected methods with faculty, and peer-review each other’s proposals. They present the methods orally to faculty and fellow-students.
- In the third week students prepare an implementation plan for the project. They develop a list of items, SOPs, worksheets, databases, etc. to develop before starting the study. They work out some SOPs in detail to include in the study proposal.
- Finally, each group submits a written study proposal, which is discussed with each student individually. It is then orally presented by the group, with supporting slides, to faculty, fellow-students and invited ITM scientists. This presentation is followed by a discussion, moderated by a peer jury composed of fellow-students who have read the presented assignment.
The overall score of each student is graded with a maximum of 100 points (60 individual and 40 group score). In order to obtain the credit certificate, a minimum of 50/100 points is required.
- E-learning: The online assessments represent 10/60 points in the individual score.
- Written proposal: 20/40 points in group score. The developed research project is evaluated by the course faculty, both on content and clarity. Different pre-defined sections will be scored: method selection, implementation plan, quality and appropriateness of supporting documents (SOPs, database, data collection forms, …). The score obtained on this evaluation is valid for each student in the group.
- Individual discussion: 50/60 points individual score. A round table is organized with 5 ITM scientists (including course faculty members) and each individual student. The assignment in which he participated is discussed, whereby the student can elaborate on his personal contribution, and can give his personal vision on the project. This will lead to an individual score on a total of 50.
- Oral presentation: 15/40 points group score. Each group presents the project with slides in 15 min, followed by 15 min of discussion. Three ITM scientists will grade the presentation. The total on 15 points is added to the score of each group member.
- Peer jury: 5/40 points group score. For each assignment, a student jury is composed. They will read the project, and will lead and moderate the discussions during the oral presentations. The three ITM scientists who will grade the oral presentations will also grade the moderation based on form and relevance of the questions. The score (5 points maximum) is given to each member of the peer jury.
In case a student fails, he/she will get the opportunity to hand in an improved written proposal, and to present this in a tele-conference, within one month after the end of the course.
- Prior education
- Relevance of work experience
- Bench experience in molecular biology, ranked as follows:
- SOP execution: student has carried out a written standard operating procedure
- Trouble shooting: student has dealt with unexpected outcomes, and solved them adequately
- SOP writing: given a protocol from literature, student has transformed it into an SOP, and carried out the experiment
- Method development: given a specific research question, student has studied literature, and based on existing knowledge has developed, evaluated and validated his own procedure.
These ranks are given for each of the following techniques: Conventional PCR (gel-based), Real-time PCR, Quantitative PCR, DNA extraction, RNA extraction, Sanger (dideoxy) sequencing and analysis, Next generation sequencing and analysis, Molecular cloning, Fragment analysis, Primer and probe development, Phylogenomics
- Students may be invited for a tele-conference call to allow a better understanding of their practical experience.
- Each student who successfully completes the e-learning part is invited to attend the face-to-face sessions.