The National Institute on Deafness and Other Communication Disorders (NIDCD) recently issued a new strategic plan that outlines the institute’s scientific priorities over the next five years. Developed through iterative collaborations with various stakeholders, the 2023-2027 NIDCD Strategic Plan: Advancing the Science of Communication to Improve Lives creates a unified vision for generating breakthroughs in areas of basic research, model systems, innovative technologies, individualized treatment approaches, scientific data sharing, and translation of research findings into clinical practice. To accelerate these scientific discoveries, NIDCD actively participates in efforts that encourage innovation through partnerships. NIDCD also supports research to better understand the normal and disordered processes of taste and smell including the molecular, cellular, and neurobiological processes underlying chemosensory processing, mechanisms of sensory cell development and regeneration, and the utility of smell tests to screen for serious health conditions. Through these and other efforts, NIDCD will continue to conduct and support research that improves the quality of life for the millions of American impacted by conditions affecting taste or smell.
The National Institute on Deafness and Other Communication Disorders (NIDCD) recently announced the release of its five-year strategic plan, with scientific priorities that include basic research, model systems, innovative technologies, individualized treatment approaches, scientific data sharing, and translation of research into clinical tools (NIDCD, 2022).
Over the last three decades, research funded by NIDCD has launched critical discoveries that have led to increasingly effective, evidence-based treatments for the millions of Americans impacted by conditions within our mission areas. To project our priorities over the next five years, the 2023-2027 NIDCD Strategic Plan: Advancing the Science of Communication to Improve Lives was developed with input from scientific experts, the NDCD Advisory Council, NIDCD staff, and the public. The result is a plan that presents a unified vision organized around six main scientific themes: (1) basic research to better understand normal function and disordered processes; (2) model systems to inform research and transform findings into more effective treatments; (3) precision medicine approaches to prevention, diagnosis, and treatment; (4) translation of scientific advances into standard clinical care; (5) biomedical data sharing; and (6) advanced technologies to improve prevention, diagnosis, and treatment (NIDCD, 2022).
Here we share a few examples of current activities in the hope of stimulating research proposals that address some of the challenges and opportunities in the chemical senses.
Despite substantial advances in the field of neuroscience, the underlying mechanisms of most neurological conditions are poorly understood due to the complexity of the human brain. NIDCD benefits from NIH-wide partnerships such as the Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative®. The BRAIN Initiative® (NIDCD, 2023b)., is a partnership among several non-federal and federal organizations, including 10 Institutes and Centers at NIH. While capitalizing on the development and application of new tools and technologies, investigators can coordinate research efforts, share critical expertise, and pool resources, thereby gaining a better understanding of how neurons and neural circuits interact in both time and space (NIH, n.d.-a).
In Fiscal Years 2021 and 2022, the BRAIN Initiative supported 20 awards focused on the chemical senses, for a total of $21 million. For example, the BRAIN Circuit Program (NIH, n.d.-d) supported a team examining potential models of odor coding to better understand what features of olfactory stimuli are represented in the brain (NIH RePORTER, n.d.-h). Another such award supported a team using computational and experimental approaches to understand sequential switching within circuits in a gustatory-focused part of the cerebral cortex (NIH RePORTER, n.d.-c). In other programs, BRAIN investigators have used animals models to visualize neuronal activity in the olfactory epithelium in response to odorants (NIH RePORTER, n.d.-e, n.d.-f, n.d.-g); employed computational modeling to develop a dynamic model of oscillation transitions in the mammalian olfactory system (NIH RePORTER, n.d.-b); explored the function of brainstem taste circuits in regulating state dependent taste coding and food intake behaviors (NIH RePORTER, n.d.-d); and investigated how the brain uses algorithmic strategies to gain insights into circuit mechanisms involved in olfactory processing (NIH RePORTER, n.d.-a). The BRAIN Initiative® makes significant investments to build the infrastructure needed to effectively share and interpret data. Due to the promotion of data standards, such as FAIR (Findability, Accessibility, Interoperability, and Reusability) principles, the research community can access BRAIN Initiative® data archives to perform secondary data analyses.
NIDCD participates in BRAIN Initiative® funding opportunities (NIH, n.d.-b), and issues its own funding notices to stimulate investigator-driven applications. For example, NIDCD recently released a notice of special interest seeking applications from interdisciplinary teams using cutting-edge technologies to advance a mechanistic understanding of the neural circuits underlying sensory processing. By capitalizing on the talents and resources of diverse teams, NIDCD aims to rapidly further our knowledge on the circuits that convey chemosensory information and how they change in response to disease, injury, age, or experience (NIDCD, 2023a, p. 23).
Taste cells and olfactory sensory neurons are renewed throughout life and can regenerate after injury, which offers opportunities to better understand mechanisms underlying recovery of sensory function after loss (Lakshmanan et al., 2022; Shechtman et al., 2021). For example, using surgical, chemical, and inflammatory models of injury in the gustatory and olfactory systems, investigators have shown that immune responses can influence the degeneration, and later regeneration, of damaged olfactory sensory neurons and taste receptor cells. The findings can contribute to a better understanding of immune-chemosensory cell interactions, which may then lead to improved therapies for taste and smell dysfunctions following injury or due to aging (Lakshmanan et al., 2022).
Although these and other findings using in vivo model systems have told us much about the renewal of taste cells and olfactory sensory neurons, there are still many unanswered questions (Barlow, 2022). In vitro approaches, such as the use of organoid models, can potentially provide convenient and cost-effective methods to explore mechanisms of human development and disease (Liu et al., 2022). In the organoid model, investigators use stem cells to generate three-dimensional tissues or organs called organoids. They use these 3-D models to explore cellular interactions and screen drugs for therapeutic and adverse effects (Guy et al., 2021). For example, investigators use taste bud organoids to model diseases such as oral mucositis; better understand the genes and signaling pathways involved in taste bud development; and explore mechanisms of taste transmission (Liu et al., 2022). Organoids derived from mouse taste stem cells are providing insights into how the different types of taste cell receptors are renewed, thereby helping investigators better understand processes underlying drug- and radiation-induced taste dysfunction (Shechtman et al., 2021).
Smell disorders may be associated with some illnesses, injuries, and diseases (NIDCD, 2014), and may be useful for screening for certain medical conditions. In particular, dysfunction in smell can be an early sign of Parkinson’s disease, Alzheimer’s disease, (Goodwin et al., 2022; NIDCD, 2014) or multiple sclerosis (NIDCD, 2014). Although smell tests by themselves are not sufficient to diagnose these conditions, they may, when combined with other tests, help identify neurodegenerative disorders before physical or cognitive impairments are seen (Goodwin et al., 2022). Even in the absence of disease-modifying treatments, earlier diagnosis may help reduce common risk factors for dementia or provide earlier access to treatments that manage symptoms (Rasmussen & Langerman, 2019).
A chemosensory disorder may also be associated with other health conditions, such as obesity, diabetes, hypertension, malnutrition, (NIDCD, 2014), and COVID-19 (Barlow, 2022). Anosmia (lack of sense of smell), hyposmia (reduced sense of smell), and dysgeusia (change in taste) have been reported in 30-80 percent of cases of adults infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). NIDCD provided supplemental funds to 18 ongoing NIDCD grants to enable investigators to address the pathology, prevention, diagnosis, sequelae, or treatment of COVID-19 (FY 2023 Congressional Justification; NIDCD, 2022; Mazzoli et al., 2021).
NIDCD recognizes the opportunity for our chemical senses investigators to benefit from participation in the National Institutes of Health’s Researching COVID to Enhance Recovery (RECOVER) Initiative (NIH, n.d.-c). RECOVER is studying people with and without COVID to help us learn why and how Long COVID affects some people and not others. RECOVER investigators also seek to develop standardized criteria for identifying Long COVID (Loreche et al., 2023; Thaweethai et al., 2023). They used machine learning to analyze electronic medical records and describe subgroups of individuals with particular Long COVID symptoms that may inform treatment and management (Zhang et al., 2023). Loss of or change in smell and taste is a common Long COVID symptom (What Is Long COVID | RECOVER COVID Initiative, n.d.). NIDCD encourages research to understand, prevent, and treat taste and smell loss due to Long COVID.
NIDCD remains committed to pooling talent and resources to advance basic and translational research to better understand the chemical senses and causes of chemosensory dysfunction. The Institute understands the frustrations of those working to treat taste and smell disorders and seeks to support the development of effective therapies to prevent, treat, and mitigate these disorders. NIDCD will continue to participate in partnerships and support research that aims to accelerate discoveries that advance our mission. I look forward to collaborating with scientists, health service providers, policymakers, and other stakeholders to advance NIDCD’s mission to conduct and support research in the normal and disordered processes of taste, smell, hearing, balance, voice, speech, and language.