Local, national, and international researchers, students, special guests, and stakeholders gathered together on October 17, 2019 to discuss project updates and the future of tick immunology and tick-borne illness research.
The first annual Symposium for the Tick Immunity project funded by the National Institute of Allergy and Infectious Diseases (NIAID) was held on October 17, 2019 at the University of Maryland, College Park. The nearly 50 attendees of the symposium represented local, national, and international scientists, researchers, students, special guests, and stakeholders working or interested in tick immunology and tick-borne illness. The Symposium not only allowed members of the tick immunology community to come together and discuss progress, goals, and future directions for the Tick Immunity project, but it also facilitated outreach to the greater community interested in tick-borne illness.
The day was buzzing with excitement for this project and the future of this work, with opening remarks from Dean Craig Beyrouty of the College of Agriculture & Natural Resources, University of Maryland, College Park, home to the lead principal investigator of the Tick Immunity project, Dr. Utpal Pal. “Everyone knows someone in this region that has been affected by tick-borne diseases, and the effects are global as well,” said Beyrouty. “The world is very concerned about the spread of infectious diseases right now, and the work that you do plays a huge role.”
Dean Beyrouty and Dr. Pal discussing the importance of the Tick Immunity project; Dr. Pal posed with Dr. Xiaoping Zhu, Chair of Veterinary Medicine at the University of Maryland, and Dean Beyrouty.
NIAID funders echoed these statements of the impact and timeliness of this project, and the great need for this work, highlighting the progression of the federal government’s interest in tick-borne illness research. “As you can see with the progression starting with the 21st Century Cures Act, tick-borne diseases are having a moment, so now is really the time to be doing this work, and I’m hoping that it is going to increase with more funding and more opportunities to do important research,” said Maliha Ilias, NIAID Lyme Disease Program Officer. In addition to the importance of outreach through Symposiums like this one and sharing all this work with the scientific and public community to further advance research and understanding of tick-borne illness, Adriana Costero-Saint Denis, the Tick Immunity Program Officer with the Vector Biology Branch of NIAID, emphasized their excitement of the training opportunities this program provides for the next generation of tick immunologists. “I’m excited to see a lot of young investigators here today because we want to support new researchers coming into this field, and this program will be a big part of that.”
The morning continued with an introduction from Dr. Pal providing an overview of the Tick Immunity project goals and objectives, and putting the project in context. With tick-borne diseases being some of the oldest diseases known to man, “Ticks know more about humans than humans know about ticks,” said Dr. Pal. “Ticks actually have very strong immune responses [to pathogens that cause diseases like Lyme and Anaplasmosis], which isn’t surprising, we just knew very little about it. So this is the goal of this project - to develop fundamental knowledge on tick immune responses.” The ultimate objective would then be to use this knowledge to help eradicate Lyme and Anaplasmosis, through the development of ticks that don’t carry the pathogens, or through the use of tick immune methods to develop immunity in humans, vaccines, and treatment strategies. Dr. Pal also discussed the goals of the Tick Immunity Administrative Core, which aims to advance and support the project through leadership and management, evaluation, training, and communication and dissemination of research through outlets such as TickImmunity.info.
Dr. Pal providing an overview of the Tick Immunity project.
Guest speakers closed out the morning, presenting pertinent perspectives to help give the Tick Immunity project additional context and further advance the investigators’ research methods. Speakers were local, national, and international, providing a wide scope of data. First, Emmanuel Mongodin, Associate Professor at the University of Maryland School of Medicine and Institute of Genome Sciences, gave insight into his work on immune system interactions with the microbiome, a key component of the Tick Immunity project. Dr. Mongodin presented techniques for examining and characterizing the microbiome, the importance of controlling for contaminants in analyses, and ways to move beyond association studies and into establishing causality.
Dr. Daniel Sonenshine, Professor Emeritus at Old Dominion University, engaging with guest speakers.
Next, Dr. Volker Fingerle, Head of the German National Reference Centre for Borrelia in Germany, shared perspectives on tick-borne diseases in Europe. Dr. Fingerle focused on differences between U.S. and European tick-borne infections, highlighting that Europe has five additional strains of Borrelia (the family of pathogens that causes Lyme disease) in Europe that are proven to be pathogenic in humans. Also, unlike the U.S. where Lyme disease and tick-borne infections are only prominent in certain geographic regions, basically the entirety of Europe is affected by tick-borne illness, with 650,000 – 850,000 cases of Lyme reported each year. Though thought to be an underestimate by many, the U.S. estimates about 300,000 cases per year. Dr. Fingerle also discussed research around the concept of chronic Lyme disease or late Lyme disease, which is a growing concern around the world and is very problematic for diagnosis and treatment.
Dr. Fingerle speaking on tick-borne illness in Europe.
Finally, keynote speaker Dr. Jason Rasgon, Professor at Penn State University, talked about applications of CRISPR gene editing technologies for arthropods, with the potential to use this technology to create genetically modified ticks. “We need to be able to make very specific changes to the genomes in order to make ticks that don’t transmit Borrelia or mosquitoes that don’t transmit malaria, and then use these tools to push genes through populations,” said Dr. Rasgon. After a discussion of the history of gene editing in arthropods and how CRISPR has changed the game allowing for very specific cuts and edits to be made in the genome, Dr. Rasgon discussed his passion for tool development. Specifically, his lab has developed an exciting technique to inject adult arthropods and ensure genetic modification is expressed in the offspring, which is much easier, cheaper, and teachable to anyone and in any setting, unlike injecting embryos which is expensive, labor intensive, and can only be applied to species that actually produce embryos. This advance is helping make this technology available around the world to advance research of all kinds, and it can be applied to ticks.
Keynote speaker Dr. Rasgon discussing CRISPR applications.
After lunch, the Tick Immunity project team took over the program, providing updates on the four major project focus areas by the four principal investigators and members of their labs. Dr. Pal and his Postdoctoral Fellow, Vipin Singh Rana, started off the afternoon with a review of Project 1, examining the indirect immune response mechanisms in ticks as they try to kill pathogens like Borrelia burgdorferi (causing Lyme disease) and Anaplasma phagocytophilum (causing Anaplasmosis). Indirect immune response involves the tick recognizing something is off with the blood meal they’ve just ingested without specifically recognizing what pathogen it may contain. The tick triggers non-specific immune defenses to kill the unidentified pathogens, and Project 1 hopes to examine this and how cross-species immunity signaling occurs through several different pathways and mechanisms. The team has identified certain proteins such as SP10 that have Borreliacidal activity, or activity to help kill Borrelia. They hope to further investigate how these proteins play a role in signaling across different immune pathways. “SP10 is very exciting with antimicrobial properties and the potential for therapeutic options and specificity studies for killing Borrelia,” said Dr. Pal.
Tick Immunity Symposium guests and participants engaging with Project 1 updates.
In Project 2, Dr. Joao Pedra and his team at the University of Maryland School of Medicine are examining direct immune response mechanisms in ticks, responses that specifically know what pathogen is in the blood meal and how the tick tries to kill that pathogen. “The tick immune system is important in many processes, among them acquisition, transmission, and persistence of pathogens,” said Dr. Pedra. Dr. Pedra started out with an overview of the distinct nature of ticks from other insects, emphasizing how important it is to work on tick immunology specifically in projects like these. “Ticks and insects are very far about, about 500 million years apart, similar to comparing fish to humans,” emphasized Dr. Pedra. Dr. Pedra then discussed the directions of their work on this project, looking at specific pathways, lipid-protein interactions, and proteins that may be important for direct immune response. Specifically, Dr. Pedra and his team are looking for what protein receptor could be responsible for sensing lipids as an important part of the signaling pathway, and a protein called Croquemort could provide some of those answers.
Dr. Pedra discussing direct immune responses in ticks.
Dr. Erol Fikrig from Yale University, his co-investigator Dr. Sukanya Narasimhan, and Postdoctoral Fellow Jesse Hwang spoke on progress in Project 3, examining how gut bacteria or microbiota interacts with immune responses in ticks to kill pathogens they ingest. “How pathogens go through the layers and biofilms inside the tick gut, and the microbes that make up the microbiome of the tick gut are relatively unknown - it is a big black box,” said Dr. Fikrig. The ultimate goal is to understand how tick microbiota interact with the different immune pathways being studied in Project 1 and Project 2. There is evidence that Anaplasma and Borrelia basically prefer opposite conditions in microbiota in the tick gut. While Borrelia prefers a healthy biofilm, microbiota, and gut function from the tick to thrive and live there, Anaplasma lives outside the gut and does things that are detrimental to the gut to ensure its survival. What happens in cases of co-infection is largely unknown and another area for future research. The team is also examining Adiponectin, a protein hormone that could be involved in immune signaling and changes in the tick gut.
To close out the day, Dr. Ulrike Munderloh and co-investigator Dr. Jonathan Oliver from the University of Minnesota spoke on behalf of the fourth project, the Tick Resources Core. The Tick Resources Core is tasked with providing reagents, instructions, cell lines, and actual ticks to the Tick Immunity team. This support is essential to work done not just in the Tick Immunity project, but beyond into tick-borne illness research as a whole. Dr. John Dumler with the Uniformed Services University, special guest and esteemed researcher in tick-borne illness, made a point of thanking Dr. Munderloh and her lab for all her work to advance the field over the years. For this project, Dr. Oliver spoke on the subject of membrane feeding techniques and how to ensure that your ticks are feeding and actually contracting the pathogens necessary to do this work. Dr. Munderloh discussed progress they have made on tick cell lines and mutant pathogens that might be important for future work in the field. “You can manipulate tick cells in culture much more easily than you can manipulate ticks,” said Dr. Munderloh. Dr. Munderloh and her team are currently working on an Anaplasma mutant library and are in the process of characterizing these mutants to ready them for distribution to labs around the world.
Dr. Fikrig and Dr. Munderloh discussing Project 3 and the Tick Resources Core, respectively.
After the open session of the Symposium ended, the Tick Immunity team had dinner and a closed discussion with their Scientific Advisory Board, comprised of senior internationally-renowned researchers in tick-borne illness. The Board includes Dr. Jorge Benach, Distinguished Professor at Stony Brook University; Dr. Marcelo Jacobs-Lorena, Professor at Johns Hopkins University; and Dr. Guy Palmer, Professor at Washington State University. The Board is charged with discussing findings, strategic planning, and providing research guidance to the Tick Immunity team.
Tick Immunity team Principal Investigators, Scientific Advisory Board, and NIAID Program Officer.
With all of this exciting progress, the Tick Immunity team is looking forward to their future work and the next Symposium, which will be held in Fall 2020 at the University of Maryland School of Medicine in Baltimore, Maryland, home of Dr. Pedra and his lab. Stay tuned for more information and developments from the project, and please reach out with any questions to tickimmunity@gmail.com.
Comments