For the 2017 Global Health Disparities Research Fellowship, you may apply to no more than two (2) of the research projects described below. Please read the descriptions carefully and ensure that you have the qualifications required to complete the project. If you have any questions, please contact the MHIRT program. Please DO NOT contact the professors directly.
BRAZIL – Prenylated Indole Alkaloids and Parasitic Diseases (1 slot)
Title: Isolation, Synthesis, and Anti-Parasitic Evaluation of Natural Products
Background: Parasitic diseases lead to disproportionately more deaths in developing countries. Unfortunately, many of the anti-parasitic medicines that are approved for use today were developed over half a century ago and have significant associated toxicity. A promising avenue to identify more effective anti-parasitics with reduced side effects is to evaluate natural products that are recognized anti-parasitics from veterinary medicine and closely related compounds that may be isolated from the same source or prepared chemically. For example, ivermectin/avermectin, first introduced to treat blood-worms in horses and dogs, emerged as an effective treatment for river blindness in the 1980s and was awarded the Nobel Prize in Physiology in 2015. Over the last decade, a derivative of the reverse-prenylated indole alkaloid compound paraherquamide called derquantel has been used effectively to rid worms of parasites in New Zealand. We are interested in investigating the effectiveness of new natural product isolates and compounds related to derquantel and paraherquamide as anti-parasitics, which may ultimately be used to address parasites in humans.
Project Description: The aim of this project is to isolate from natural sources and prepare chemically, natural products and compounds related to the paraherquamides and derquantel. These materials will be screened for anti-parasitic activity. The project will focus on the ability to purify and elucidate structure using instruments such as HPLC and techniques such as NMR. The MHIRT student will learn how to carry out chemical synthesis of natural products and participate in the isolation and structural characterization of these antiparasitic molecules. The chemical synthesis aspects will be carried out in the Sarpong group at UC Berkeley and the isolation of new entities and their initial antiparasitic evaluation will be conducted in the Berlinck laboratory in Brazil.
Required Qualifications: Advanced undergraduates or graduate students in the Department of Chemistry will have the appropriate background to complete this project.
International Site: The partner site for this project is the Berlinck laboratory at the Instituto de Química de São Carlos Universidade de São Paulo. Prof. Berlinck is an internationally recognized natural product isolation chemist with expertise in the isolation, characterization and biological evaluation of secondary metabolites.The Sarpong laboratory and the Berlinck laboratory have collaborated productively and published a joint paper already (Nature 2014, 509, 318). The Berlinck laboratory is equipped with all the necessary tools and equipment that are required for conducting modern natural product isolation and characterization (HPLC, mass spectrometers etc.). The visiting student will be paired with a senior graduate student in the Berlinck lab to learn about how to conduct research effectively in the laboratory. Following an appropriate period, the student will take on an independent project where they will consult with the graduate student member and Prof. Berlinck on a daily and weekly basis, respectively. It is anticipated that Prof. Berlinck will dedicate approximately 10% of his time to these interactions.
BRAZIL II — Bacterial Infections (1 slot)
Lee Riley & Claudete Cardoso, Sergio Arruda, Beatriz Moreira
Background: The Riley laboratory has been involved in collaborative projects in Brazil since 1990. The collaboration has focused on infectious diseases of importance to urban centers, specifically on infectious diseases of urban slums. Brazil has undergone more than 350% increase in its urban population since 1960. This has engendered completely new types of health problems with magnitude not seen in most developing or developed countries. Urbanization and the explosive increase in shantytown populations have created a new set of health problems: chronic infectious (TB, AIDS, post-infectious cardiovascular and renal diseases) and non-infectious diseases (hypertension, diabetes, asthma, and unintentional and unintentional injuries). A single placement with the Riley lab will be available in Brazil, but the particular project and site will be negotiated once a student joins the lab. The options are outlined below.
Possible Project 1: Biomarkers for TB diagnosis and monitoring response to treatment (Oswaldo Cruz Foundation, Salvador; collaborator-Cardoso): Exploiting the knowledge gained from basic TB pathogenesis research conducted at UC Berkeley, we are evaluating immunological responses in patients with latent infection, to determine responses predictive of those who may progress to active disease. In particular, we are exploring host response to M. tuberculosis lipids as biomarkers for infection and response to treatment for TB. This is done in collaboration with researchers at Oswaldo Cruz Foundation in Salvador, Brazil. This project will require some experiences working in a laboratory, especially with immunology procedures.
Possible Project 2:Biomarkers for pediatric TB diagnosis (Federal University of Fluminense, Rio de Janeiro; Collaborator–Arruda): Pediatric TB diagnosis is complicated by the fact that small children cannot expectorate sputum. Hence, samples containing M. tuberculosis cannot be readily obtained. We have identified several candidate biomarkers that may be detected in blood by simple ELISA. Samples from children with and without TB will be obtained to validate the biomarker assay. This project will require experiences in working in a laboratory and familiarity with immunology procedures.
Possible Project 3: Drug-resistant Gram-negative bacterial infections (Federal University of Rio de Janeiro; Collaborator–Moreira): Hospital infections are a major emerging problem in Rio de Janeiro as well as in other major cities of Brazil. For the last 15 years, we have been conducting molecular epidemiologic studies with the Federal University of Rio de Janeiro, to understand risk factors for transmission and characterize pathogens implicated in infections in a large university hospital in Rio. This project will require some experiences in microbiology research.
BRAZIL III— Zika Epidemic (1 slot)
Lee Riley & Claudete Cardoso
Background: The Riley laboratory has been involved in collaborative projects in Brazil since 1990. The collaboration has focused on infectious diseases of importance to urban centers, specifically on infectious diseases of urban slums. In 2015, Brazil became the first country in Latin America to experience the explosive epidemic of Zika virus infections. Subsequently, Zika virus infection in fetus has been shown to cause a severe congenital neurologic disease microcephaly. Microcephaly cases are currently occurring in Brazil in epidemic proportions.
Project Description: The Riley Lab in collaboration with a Brazilian pediatric infectious disease researcher Dr. Claudete Cardoso of Federal Fluminense University has begun a prospective study of newborns whose mothers were exposed to Zika virus during pregnancy. This is part of a pediatric cohort study that includes biomarker assessment for the diagnosis of pediatric TB. Over the next 2 years, we will create a cohort of newborns with normocephaly whose mothers were exposed to the Zika virus during pregnancy. This cohort will be prospectively followed for cognitive and developmental abnormalities.
International Site:The Federal University of Fluminense is one of the largest universities in Brazil, and has been experiencing a huge growth in the number of undergraduate and post-graduate courses, as well as in research and extension activities. The academic arena, the university offers to its students scientific initiation, innovation, monitoring and internship.
Required Qualifications: This project will require working knowledge of Portuguese or Spanish, and experiences performing ELISA and PCR.
CHINA I – HIV Transcription Activation and Latency Reversal (2 slots)
Title: Functional characterization of novel Tat partners key for activation of HIV-1 transcription and exit from latency.
Background: We are interested in elucidating the mechanisms and identifying host cellular co-factors that control HIV-1 transcription and latency. It was 15 years ago when the human transcription elongation factor P-TEFb was first identified as a host cofactor for activation of HIV-1 transcription by the viral encoded Tat protein. Recruited by Tat to the viral LTR, P-TEFb stimulates RNA polymerase II elongation, a process essential for viral replication. Since 1997, this landmark discovery has provided the basic framework for our understanding of Tat function during the HIV life cycle, and P-TEFb remains the only widely accepted functional Tat partner till this day. However, published data suggest that Tat-transactivation involves more than the interaction between Tat and P-TEFb. A major effort of ours is thus aimed at identifying additional cellular factors that may associate with Tat-P-TEFb to further enhance Tat-transactivation.
Project Description: Recently, our laboratory has successfully identified the first new Tat partners in more than a decade. These partner proteins together with P-TEFb exist in a preformed complex called the Super Elongation Complex. The MHIRT research apprentice will use a combination of molecular and biochemical techniques to characterize this complex and determine the mechanism by which it cooperates with Tat to stimulate HIV-1 transcription and exist from latency. A portion of this project will be conducted in our collaborator’s lab, led by Dr. Yuhua Xue at Xiamen University in China.
International Site: The partner for this project is Dr. Yuhua Xue in the School of Pharmaceutical Sciences at Xiamen University, China. Xiamen University has standard training and educational programs in place for international students at both the undergraduate and graduate levels. The visiting student will first be paired with a senior graduate student or a postdoc in the lab in order to become familiar with the daily operations in the lab.
Required Qualifications: Advanced undergraduates or graduate students in MCB will have the appropriate background to complete this project.
CHINA II– Data Science for Advancing an Environmental Understanding of Infectious Disease Dynamics(2 slots)
Justin Remais (UC Berkeley) & Changhong Yang (China Centers for Disease Control and Prevention)
Title: Methods for investigating the interaction between environmental change and waterborne, vector-borne and parasitic diseases in China
Background: This project — part of a recently funded NSF Water, Sustainability, and Climate grant — aims to develop computational approaches for better understanding and responding to infectious disease risks that result from a changing and more variable climate. Graduate or undergraduate students contributing to this project will advance methods to characterize dynamics of key infections in the presence of changes in water resources induced by climate change.
Project Description: Members of our team will be embedded in the Institute for Public Health Informatics at the China Centers for Disease Control and Prevention, where they will query and analyze high dimensional surveillance data streams on the dynamics of malaria, dengue, schistosomiasis, Japanese encephalitis and leptospirosis. Graduate or undergraduate students contributing to this project will investigate the social and environmental dynamics that mediate the dynamics of these infections in China — for instance, examining the effects of extreme climatic events on the transmission of leptospirosis in flood-prone rural areas — and will acquire and analyze ‘Big’ surveillance data drawn from China’s massive NIDR system in order to do so. Other activities include the development of tools for the characterization and optimization of infectious disease surveillance networks using both epidemiological analysis and simulation science. Undergraduate, Master’s thesis and doctoral-level research opportunities are available within the group.
International Site: These studies are being carried out in collaboration with the Institute for Public Health Informatics at the China Centers for Disease Control and Prevention in Chengdu, Sichuan Province, PRC. The interns will be supervised by Dr. Changhong Yang, the director of the institute, as well as by Professor Remais and his scientific staff.
Required Qualifications: Undergraduate or graduate training in quantitative science is desirable, such as mathematics, modeling and simulation, computer science, environmental science, dynamical systems, engineering, population biology, or infectious disease epidemiology, although successful group members in the Remais Lab also have had backgrounds in physics, biology, anthropology and medicine. Technical skillsets, such as geospatial analysis, GIS, time-series, differential equations, programming in any language (we are known to use R, Python, Matlab, Ruby, Perl, C, etc.), hydrological modeling, theoretical ecology, or remote sensing, would be additionally desirable; effective written and verbal communication are essential.
CHINA III—Tuberculosis and Diabetes (1 slot)
Lee Riley, UC Berkeley & Beibei Wu, Zhejian Provincial Centers for Disease Control
Title: Impact of Tuberculosis on Diabetes
Background: The Riley laboratory has initiated a new project to examine the impact of diabetes on tuberculosis in Hanzhou, China in collaboration with the TB Laboratory Section of the Zhejian Provincial CDC.
Project Description: The main goal of this project is to develop new laboratory tools and contribute to new understanding of how tuberculosis (TB) manifests among those who have type 2 diabetes mellitus (DM) in Zhejiang Province in China. China now leads the world in DM prevalence, and it ranks third in the estimated number of new TB cases reported each year. DM can greatly accelerate the occurrence of TB. We do not know why or how DM increases the occurrence of TB. An individual with DM may have weakened immunity that, if newly infected with the agent of TB Mycobacterium tuberculosis, could rapidly progress to TB (called recent-transmission TB). If he is latently infected with M. tuberculosis to begin with and later develops DM, his latent infection could reactivate to cause disease (reactivation TB). DM can also increase the chance of an individual who completes treatment for TB to have recurrent TB due to either relapse from the original infection (relapse TB) or from a new infection (reinfection TB). These outcomes could also be affected by socioeconomic, demographic, and epidemiologic factors. In China, because more than 70% of new TB cases are caused by a strain belonging to a single lineage called Beijing clade, the traditional epidemiologic and genotyping tests to distinguish these clinical outcomes of TB cannot be used. It is critical for a national TB control program to have accurate data on the relative proportion of these outcomes to prioritize its control strategy. This project will address this challenge by aiming to 1) develop a new genotyping test that can more accurately distinguish these four outcomes, 2) identify demographic, social, behavioral, environmental , nutritional, and clinical characteristics associated with these outcomes, and 3) identify host biosignatures associated with new-transmission TB, reactivation TB, and relapse TB among diabetics compared to non-diabetics.
Required Qualifications: This project will require working knowledge of Mandarin (or Shanghainese).
INDIA — Public Health Research Institute of India (PHRII) (2 slots)
Title: Molecular and Field Epidemiology Studies with Woman and Child Cohorts in Mysore, India
International Site Information: Public Health Research Institute of India (PHRII) is a Charitable Trust focused on public health research and evidence based care for women and children in India. Located in Mysore, the second largest city in Karnataka, PHRII has established collaborations with University of California, Berkeley; JSS University, National Rural Health Mission (NRHM); Karnataka State AIDS Control Society, and the Positive Women’s network. The organization has a full service diagnostic laboratory, a reproductive health clinic in central Mysore City, and mobile clinics serving rural areas of Mysore District.
Currently, some of the ongoing projects at PHRII include:
- Mental health issues in pregnant and postnatal women;
- Prevention of vertical transmission of HIV;
- Under 5-child mortality among disadvantaged populations in remote tribal and rural areas;
- Cognitive and mental development of infant and relationship to maternal mental health;
- Primary and secondary prevention of cervical cancer;
- Development of diagnostics for cancer screening and gestational diabetes;
- Understanding risk behaviors among emerging adults;
PHRII’s research collaboration with UCB Riley Laboratories has focused on the pathogenesis of infectious and chronic diseases; molecular epidemiology on tuberculosis and drug-resistant gram-negative bacterial infections; field epidemiology and slum health.
Project Description: Candidates may select from a variety of ongoing projects in the areas described above including field based and/or laboratory work at PHRII in Mysore, India. Specific project selection will occur following the selection process and upon mutual agreement of the PIs and candidate. Interested applicants may seek additional information about available projects via Dr. Madhivanan who can be reached via the MHIRT office.
Required Qualifications: Preference will be given to candidates who have analytical skills, molecular microbiology or field experience and have worked in international settings before.
NICARAGUA – Zika in Nicaragua (2 slots)
Title: Zika Virus Infection in Nicaragua
Background: In 2015/16, Zika virus (ZIKV) of the Flavivirus genus caused explosive epidemics that began in Brazil and spread throughout the Americas. Zika rapidly became a global concern, as it has been linked to severe congenital birth defects, including microcephaly and mis¬carriage, prompting the WHO to declare the ZIKV pandemic a Public Health Emergency of International Concern in February of 2016. As of June 30, 2016, 50 countries are reporting active mosquito-borne ZIKV transmission. Over 2,500 cases have been reported in the US and its territories, with 14 confirmed cases of sexual transmission. Some of the affected countries have reported increased numbers of congenital birth defects and Guillain-Barré syndrome (GBS) cases. Acute ZIKV infection is associated with inapparent or mild symptoms, ranging from myalgia, arthralgia, low-grade fever, conjunctivitis, maculopapular rash, and headache, to prostration. While the link between ZIKV infection among pregnant women and congenital defects such as microcephaly has been deemed likely, it has not been confirmed in long-term prospective cohort studies. Further, little is known about the clinical presentation of Zika among pregnant women or long-term sequelae in children, nor about pathogenic mechanisms or anti-ZIKV immune responses. No effective ZIKV antivirals or vaccines currently exist. Nicaragua reported its first Zika case in January of 2016. Since then, Dr. Eva Harris and long-term collaborators at the Ministry of Health and Sustainable Sciences Institute in Managua, Nicaragua, have been conducting a series of investigations of Zika infection and disease in a pediatric cohort study, a pediatric hospital-based study, a household transmission study, and starting in Fall of 2016 in pregnant women and their infants. Numerous virological, molecular biological, and immunological studies are ongoing.
Project Description: We aim to describe the Zika epidemic in Nicaragua by collecting information about likely risk factors and analyzing blood samples of individuals with Zika-like symptoms through a retrospective serological study. The samples analyzed are captured as annual sample collection as part of an ongoing community-based pediatric cohort study. The project includes determining previous ZIKV infection via enzyme linked immunosorbent assay (ELISA), as well as correlating these results with associated risk factors using the survey administered to each participant. Regarding the Zika household transmission study and the Zika in Infants and Pregnancy (ZIP) study, samples need to be processed via molecular biological and serological techniques to diagnose ZIKV infection and analyze the immune response.
International Site: Our foreign research site is embedded within the Ministry of Health of Nicaragua and administered in collaboration with the Sustainable Sciences Institute (SSI). Placement is available at the National Virology Laboratory of the National Center for Diagnosis and Reference (CNDR) of the Ministry of Health. The site is well-established, with over 60 study employees, and serves several large prospective studies of dengue, chikungunya, influenza and Zika. Numerous MHIRT, MPH, and PhD students have been hosted by SSI and the National Virology Laboratory in Managua. Dr. Harris has been collaborating productively with the Nicaraguan CNDR/Ministry of Health for over 28 years.
Required qualifications: Motivated undergraduate or graduate students with Spanish language proficiency. Previous laboratory experience, particularly molecular biology, required. STATA/SAS experience preferred, but not required.
Title: From asymptomatic parasitemia to cerebral malaria – investigating causes for a wide spectrum of malaria infection outcomes
Background: Our group has performed clinical, epidemiologic and translational research on malaria infection in Blantyre, Malawi for the past 30 years. The collaboration is between Michigan State University (MSU), Queen Elizabeth Central Hospital and the University of Malawi College of Medicine, with collaborative efforts based at several other US and UK based institutes. Our focus has historically been on severe disease with a long standing observational study on children with cerebral malaria being the ‘backbone’ of our research efforts. Recent efforts have moved away from the hospitalized patient and into the community where we are investigating the role of asymptomatic malaria infection and its role in maintaining a disease transmission reservoir.
Project Description: Topics of investigation may range from clinical to epidemiologic to basic science aspects of malaria infection and its consequences. We are specifically interested in the host and/or parasite factors that lead to varied clinical outcomes after Plasmodium infection. Techniques could range from immunologic to entomologic to molecular and genetic.
International Site: The project will be based in Blantyre, Malawi at the University of Malawi College of Medicine campus. Infrastructure in Blantyre includes a Pediatric Research ward for inpatient care, a Molecular and Genomics Core laboratory, a fully functional insectary, and several well-characterized rural sites within a 60km radius.
Required Qualifications: Students currently studying biology or public health are preferred.
UGANDA – Translational Research in Malaria (1 slot)
Title: Investigating parasite and host factors associated with clinical malaria outcomes.
Background: Our group performs clinical and translational research on malaria and other infectious diseases in Africa, at UCSF and at Dominican University of California. The team at UCSF also includes Grant Dorsey and Bryan Greenhouse (Division of Infectious Diseases, Dept. of Medicine) along with many collaborators at Makerere University. This ongoing collaboration is formally known as the Makerere University-UCSF Uganda Malaria Research Program.
Project Description: Topics may include clinical, epidemiology, or molecular aspects of malaria research. In particular, we are interested in predictors of and mechanisms of drug resistance, antimalarial immune responses, and parasite-host markers of severe malaria. Other studies in Uganda involve surveillance of malaria at rural locations across the country.
International Site: This study is based in Kampala, Uganda, at the Molecular Research Laboratory (Molab) located in the New Mulago Hospital Complex. This is a long running partnership between researchers at UCSF and Makerere University in Kampala, Uganda. Additional studies take place in Tororo, Uganda. Please see http://www.muucsf.org for more information.
Required Qualifications: Students currently studying biology or public health are preferred.