A global data base of transmission trees

Infectious diseases propagate along networks of contacts of infected hosts. Increasingly, epidemiological investigations have used molecular analysis and case investigation to reconstruct these infection paths, which are then quantified as “transmission trees”. Findings from such studies have shown that features like contact structure, heterogeneity, and the presence of “super spreaders” may be crucial to the propagation and containment of epidemics. Presently, such research is primarily case-based and there is no global understanding of the ubiquity of such features across epidemics more generally. The goal of this project is to develop the first comprehensive data base of transmission trees. The student will compile data from the published literature into a common format. These data will be analyzed to look for patterns in transmission that may be generalized to other epidemics. The work will be performed using the scientific programming language R.

Host Lab: John Drake
Project type: Quantitative/Computer-based

Development of infectious disease research and teaching software

Using computer models to study infectious diseases can be challenging for students and researchers who are not trained as modelers. To make this process easier, we have developed several software packages, implemented in the popular R language, to help individuals learn about and analyze infectious disease models both at the individual and population level. The goal of this project is to further advance this software by implementing new features, making tutorials, testing existing features, etc. This will increase the usefulness and power of the software and will give future students and researchers better tools to learn about and analyze different infectious diseases. This project is quantitative. We will make use of the R language for all parts of this project. The project is offered by the Handel group:

Host Laboratory: Andreas Handel
Type of project: Quantitative/Computer-based

Data analysis to help inform norovirus vaccine design

Norovirus is a common cause of gastrointestinal disease. There is currently no vaccine, but several are under development. It is not clear how exactly a new norovirus vaccine should look like and to whom it should be mainly given (e.g. children or adults). Together with colleagues at Emory University, we are working on a project that analyzes different types of norovirus data to develop a comprehensive mathematical modeling framework to guide norovirus vaccine design and implementation. For this project, you will help with those analyses. The results of this analysis will allow us to better understand properties of norovirus infection and transmission and therefore will help inform the design and implementation of a future norovirus vaccine. This project is quantitative. We will make use of the R language for all analyses.

Host Laboratory: Andreas Handel
Type of project: Quantitative/Computer-based

Studying the relation between vaccine dose and outcomes

For every vaccine, the amount of the antigens of the pathogen one wants to vaccinate against is an important part. This amount that is currently not systematically determined but is instead based on sparse clinical data. We recently developed a framework that combines this data with mathematical models to better determine the vaccine dose that would lead to optimal outcomes. The goal of this project is to further advance this framework by combining data and computer models to determine what the impact of vaccine dose is on outcomes such as side effects and immune protection. This information will be useful for improved design of future vaccines. This project is quantitative. We will make use of the R language for all analyses.

Host Laboratory: Andreas Handel
Type of project: Quantitative/Computer-based

Exploring Effects of Abiotic and Biotic Environmental Factors in the Human Malaria System

Mosquitoes are the deadliest organism in the world, taking out approximately 725,000 people annually due to the infectious organisms they transmit to humans. The principle pathogen that contributes the most human mortality is the human malaria parasite. The transmission of malaria parasites is linked inextricably to the biology of the mosquito vector and occurs in environments where mosquitoes and parasites are exposed to a suite of biotic and abiotic factors that vary considerably over time and space. In order to better understand the net outcome of the mosquito-parasite interaction in the field, and better predict the likely performance of mosquito control tools, it is necessary to begin to consider environmental context. For example, it could be that environmental factors play a small role, simply adding ‘noise’ to the system. Alternatively, environmental factors might massively shape the outcome of vector-parasite interactions and dominate the effectiveness of novel control tools. We are interested in an REU student that is willing to combine both empirical work in the lab with computational approaches to assess the relative influence of key environmental factors (e.g. temperature, relative humidity, mosquito microbiota) on mosquito life history traits and parasite traits relevant for predicting transmission. Example projects that could be developed include the effect of microbiota and relative humidity on mosquito life history traits and transmission or the role of transgenerational imprinting of environmental cues on these traits. This work will occur in the Indian malaria mosquito (Anopheles stephensi) and human malaria (Plasmodium falciparum) system. This student will be mentored by Drs. Ash Pathak (Infectious Diseases) and Courtney Murdock (Infectious Diseases & Odum School of Ecology).

Host Laboratory: Courtney Murdock, mentored by Ash Pathak
Type of Project: Combination of Empirical/Laboratory-based and Quantitative/Computer-based

 

Exploring links between mosquitoes, the environment, and disease transmission

The Asian tiger mosquito, Aedes albopictus is one of the most highly invasive mosquito species seen to date.  The physiological and ecological plasticity of Ae. albopictus has led to its rapid global expansion.  Additionally, its ability to vector a wide-range of recently emerging arboviruses, such as dengue and Chikungunya, make it a significant public health threat.  The transmission of many mosquito-borne pathogens is strongly influenced by environmental temperature due to effects on the physiology of the insect vector and the pathogen.  Therefore, changes in local environmental conditions could significantly impact the distributions and dynamics of a range of mosquito-borne diseases.  Predicting the extent of possible changes in disease dynamics will require a detailed understanding of how a suite of mosquito-pathogen traits respond to variation in environmental temperature and other biotic factors. Projects can explore the following potential questions: 1) what are the microclimate conditions mosquitoes experience in the larval environment and relevant transmission settings?, 2) how does thermal variation influence mosquito life history traits relevant for transmission (e.g. larval development rates, larval survival, adult longevity)?, 3) can we use remotely sensed data to predict relevant mosquito microclimate?, or 4) what factors contribute to Ae. albopictus oviposition behavior and density-dependence in the larval environment. We are looking for two REU students that are interested in combining field work with computational approaches to carry out projects in the Athen’s system this summer mentored by Drs. Courtney Murdock (Infectious Diseases & Odum School of Ecology) and Craig Osenberg (Odum School of Ecology).

Host Laboratories: Courtney Murdock and Craig Osenberg
Type of Project: Combination of Empirical/Field-based, and Computational/Computer-based

Genomics of bacterial symbionts to determine nutritional roles in plant-sap feeding insects

Adelgids are sap-sucking insects that exhibit complex life cycles. Plant sap is a poor nutrient source for insects to feed upon, so many insects engage in obligate relationships with bacterial endosymbionts that play nutritional roles in synthesizing nutrients unavailable or in low quantity from the plant-sap diets of their hosts. However, the contributions of bacterial symbionts to adelgid nutrition is currently unknown on a family-wide scale. This project will involve working with a graduate student to characterize genomes from adelgid insects, including the use of high-performance computing to quality-check raw sequence data, followed by assembly and annotation of bacterial genomes. Comparison of the nutritional roles of bacterial symbionts between adelgid species may reveal that the symbionts are influenced by the complex lifestyles of the insects, an evolutionary process that has not been described to date but could be important in many organisms.

Host laboratory: Gaelen Burke
Type of project: Quantitative/Computer-based

Declining water quality associated with failing water infrastructure

Globally, failing water infrastructure has been linked to declining water quality and increased exposure to contaminants, and potentially harmful bacteria infections including, but not limited to Escherichia coli. To assess temporal and spatial changes in the chemical and bacterial composition of water associated with failing water infrastructure in watersheds in Atlanta, members of the Capps Lab will conduct a field- and lab-based empirical study. Field activities will be conducted in Atlanta, GA in stream reaches that have been sampled sporadically since the 1970’s. In conjunction with the Principal Investigator and a UGA-based graduate student, the participating student will be trained to collect and analyze water quality samples to begin relating in-stream environmental conditions with water infrastructure. Results will be applied to ongoing and future research projects in the Capps Lab. Applicants should have some previous experience conducting field research in aquatic ecology and an interest in learning techniques in analytical chemistry. Successful candidates will be expected to work effectively individually in the lab and within a team environment in urban environments in the southeast during the summer. Though hiking will be limited, in order to access the field sites, candidates should be able to walk/wade through streams for at least 1 mile while carrying up to 30lbs.

Host laboratory: Krista Capps
Type of project: Empirical/ Field and laboratory-based

Do parasites impair the fight-or-flight reactions of their hosts? Experimental investigations of beetles infected with nematodes

Temporary stressors are a part of life in the animal kingdom, whether they be encounters with predators, transient anthropogenic disturbances or severe weather events. All animals must therefore be capable of dealing with such stressors to ensure their survival, which is the ‘fight-or-flight reaction’. A number of recent research studies, across a range of animal taxa, have found that certain parasites can affect how their hosts deal with these stressors.

In the Davis lab, students have recently conducted a variety of experiments using a common beetle species, the horned passalus (pictured), which is host to a nematode called Chondronema passali. Recent work has shown parasitized beetles have reduced physical strength, cannot fight as well as non-parasitized individuals, and importantly, their stress reactions appear to be affected.

In summer 2019, a project is planned where an REU student will conduct a series of benchtop lab experiments that will all attempt to identify how parasites influence the ability of their hosts to deal with an acute stressor. This will involve field-collection of beetles (from the surrounding area), bringing them to the lab and performing behavioral experiments with them over the summer. The experiments will primarily focus on monitoring changes in stress levels of beetles before and after application of non-lethal stressors.

The ideal student for these projects will be someone who is comfortable handling insects and performing icky dissections, and who can work well in the tick- and chigger-infected field (forest habitats).

Host laboratory: Andy Davis
Type of project: Empirical/Laboratory-based

Intracellular stage of Bordetella spp.: A path to escape immune recognition

Data published by our group and others, show Bordetella pertussis, B. bronchiseptica and B. parapertussis, can survive and grow intracellular in macrophages and lung epithelial cells. These two aspects have great clinical implications. Intracellular survival could explain vaccine failure (evasion of immune recognition) as well as the long persistence period of clinical disease (disease is reported in adolescent and young adults). This project involves an exceptional opportunity to study all the molecular basis and mechanisms involved in the intracellular survival and replication of Bordetella spp. that can be responsible of the re-emergence, dissemination, lethargy periods, evasion of the immune system, vaccine failure and even transmission.

To understand intracellular survival/growth of Bordetella spp., we propose the following aims:
Aim 1: Identify genes required for specific stages of intracellular survival and replication (intracellular stage).

We will create and screen a transposon library to identify all genes required for survival and replication within macrophages.
Student role: The student will do the transposon library for Bordetella pertussis. Also, the student role in this aim it will be to screen the transposon library of Bordetella bronchiseptica and Bordetella pertussis, using the gentamicin assay and variations of it in order to identify mutations that promote survival / growth within mcarophages.

Aim 2: Define the mechanisms involved during in vitro Bordetella spp. intracellular survival and replication.

Intracellular survival and replication requires to perform several steps; a) adhere, b) invade, c) survive intracellularly, d) obtain nutrients to replicate, and e) avoid killing the host cell (i.e. inducing its apoptosis or targeting it for killing by immune cells). In this specific aim we will examine which of these aspects each mutation affects.
Student role: The student will do immunofluorescence and western blot in order to identify the localization of Bordetella spp. within macrophages, in order to determine if Bordetella can growth within macrophages and to reveal how many of the Bordetella that are engulf are death or alive within macrophages  (this techniques will require microscopy and/or flow cytometer). The student also will perform and develop western blot techniques that will identify the mechanism that Bordetella uses in order to kill macrophages.

Understanding how Bordetella species survive and grow within host cells is likely to shed light on the current problem of the high rates of vaccine failure as well as its re-emergence, as current vaccines do not induce Th1 immunity and are not effective against intracellular bacteria. This work will also reveal key genes contributing to intracellular growth/survival that can provide targets for the next generation of vaccines and therapeutics.

Host Lab: Eric Harvill
Type of project: Empirical/Laboratory-based\