Author Interviews, Genetic Research, PNAS, UCSD / 20.04.2023
We Are Able to See Thanks to a Protein Acquired from Bacteria
MedicalResearch.com Interview with:
Chinmay Kalluraya
a Selma and Robert Silagi Award for Undergraduate Excellence winner
UC San Diego and now a graduate student at MIT
and
Matt Daugherty Ph.D
Associate Professor
University of California, San Diego
Department of Molecular Biology, School of Biological Sciences
La Jolla CA, 92093-0377
MedicalResearch.com: What is the background for this study? Would you explain the role of retinoid-binding protein?
Response: We were broadly interested in discovering instances of bacterial genes that have been acquired by diverse animal genomes over millions of years of evolution by the process of horizontal gene transfer (HGT). Since these events are quite rare and most previous discoveries have been serendipitous, we developed computational methods to identify genes acquired by HGT in animals. One of the exciting discoveries from our work was that vertebrate IRBP appeared to have originated in bacteria and is now a critical component of the vertebrate visual cycle, so this paper focuses on that one discovery.
IRBP or interphotoreceptor retinoid binding protein is an important protein present in the space between two major cell types in our eyes, photoreceptor cells and RPE cells. Our ability to see involves an intricate set of steps where light is first sensed by causing a change (isomerization) in the chemical structure of molecules in the eye called retinoids. This sensing of light occurs in our photoreceptor cells. Following this change in the chemical structure, the retinoid needs to be recycled back to the chemical structure that can again sense light. This recycling occurs in RPE cells. IRBP performs the essential function of shuttling retinoids between the photoreceptors and the RPE cells, which allows the cycle of sensing and regeneration to work. Supporting its importance, mutations in IRBP (also known as retinol binding protein 3 or RBP3) can cause several severe human eye diseases.
Response: We were broadly interested in discovering instances of bacterial genes that have been acquired by diverse animal genomes over millions of years of evolution by the process of horizontal gene transfer (HGT). Since these events are quite rare and most previous discoveries have been serendipitous, we developed computational methods to identify genes acquired by HGT in animals. One of the exciting discoveries from our work was that vertebrate IRBP appeared to have originated in bacteria and is now a critical component of the vertebrate visual cycle, so this paper focuses on that one discovery.
IRBP or interphotoreceptor retinoid binding protein is an important protein present in the space between two major cell types in our eyes, photoreceptor cells and RPE cells. Our ability to see involves an intricate set of steps where light is first sensed by causing a change (isomerization) in the chemical structure of molecules in the eye called retinoids. This sensing of light occurs in our photoreceptor cells. Following this change in the chemical structure, the retinoid needs to be recycled back to the chemical structure that can again sense light. This recycling occurs in RPE cells. IRBP performs the essential function of shuttling retinoids between the photoreceptors and the RPE cells, which allows the cycle of sensing and regeneration to work. Supporting its importance, mutations in IRBP (also known as retinol binding protein 3 or RBP3) can cause several severe human eye diseases.
Dr. Potter[/caption]
MedicalResearch.com Interview with:
Kelly Potter, PhD, RN, CNE
T32 Postdoctoral Scholar
CRISMA Center, Department of Critical Care Medicine
University of Pittsburgh
MedicalResearch.com: What is the background for this study?
Response: While it is well-recognized that survivors of critical illness often experience persistent problems with mental, cognitive, and physical health, very little is known about how these problems (collectively known as post-intensive care syndrome (PICS)) affect resumption of meaningful activities, such as driving.
Dr. D'Orsogna[/caption]
Maria-Rita D'Orsogna Ph.D.
Professor, Mathematics
California State University, Northridge
Adjunct Associate Professor
Department of Computational Medicine at UCLA
MedicalResearch.com: What is the background for this study?
Response: Drug overdose deaths have been increasing in the USA for the past two decades. A ‘third wave’ of overdose fatalities started in 2013, with a shift from prescription opioids towards synthetic ones, in particular illicit fentanyl.
To examine trends in drug overdose deaths by gender, race and geography in the United States during the period 2013-2020, we used an epidemiological database provided by the Centers for Disease Control and Prevention, extracting rates by race and gender in all 50 states plus the District of Columbia. We considered the impact of four main drug categories psychostimulants with addiction potential such as methamphetamines; heroin; prescription opioids and synthetic opioids such as fentanyl and its derivatives.
Dr. Koh[/caption]
Andrew Y. Koh, M.D.
Associate Professor, Pediatrics and Microbiology
Dr. Mosley[/caption]
Jonathan Mosley, MD, PhD
Associate Professor
Division of Clinical Pharmacology
Departments of Internal Medicine and Biomedical Informatics
Vanderbilt University Medical Center
MedicalResearch.com: What is the background for this study?
Response: Prostate cancer is an important source of morbidity and mortality among men. Earlier detection of disease is essential to reduce these adverse outcomes. Prostate cancer is heritable, and many single nucleotide polymorphisms (SNPs) associated with disease risk have been identified. Thus, there is considerable interest in using tools such as polygenic risk scores, which measure the burden of genetic risk variants an individual carries, to identify men at elevated risk of disease.
Dr. Tsirigos[/caption]
Aristotelis Tsirigos, Ph.D.
Professor of Medicine and Pathology
Co-director, Precision Medicine
Director, Applied Bioinformatics Laboratories
Dr. Roca[/caption]
Anna Roca PhD
MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine
Fajara, The Gambia
MedicalResearch.com: What is the background for this study?
Response: Context specific interventions are needed to decrease the high burden of severe neonatal morbidity and mortality in sub-Saharan Africa. Severe bacterial infections are a main cause of neonatal mortality in the continent. Oral intra-partum azithromycin is a cheap intervention easily scalable. Before embarking on this trial, we conducted a proof-of-concept trial that showed the intervention reduced maternal and neonatal bacterial carriage of the most prevalent bacteria causing neonatal sepsis in the continent.
Dr. Gaudino[/caption]
Mario FL Gaudino, MD, PhD, MSCE, FEBCTS, FACC, FAHA
Dr. Stevermer[/caption]
James Stevermer, M.D., M.S.P.H.
Vice chair for clinical affairs
Professor of family and community medicine
University of Missouri
Medical director of MU Health Care Family Medicine–Callaway Physicians,
Dr. Stevermer joined the U.S. Preventive Service Task Force in January 2021.
MedicalResearch.com: What is the background for this study?
Response: Genital herpes is a common sexually transmitted infection (STI) that unfortunately has no cure and cannot accurately be detected in people who do not have signs of the condition. The current screening tests have limitations and there is a high chance that test results will say a person has the condition when they do not. In addition, the available treatments are focused on managing symptoms and preventing the condition from reoccurring. As a result, the Task Force concluded that the harms of screening outweigh the benefits.
Dr. Mahdavi[/caption]
Dr. Sara Mahdavi, PhD
Clinical Scientist and Clinical Instructor
Research Appointment in the Faculty of Medicine
University of Toronto
Toronto, ON
MedicalResearch.com: What is the background for this study?
Response: This was a long-term study spanning 16 years and began with a population of young adults who were medically assessed on a regular basis. It was remarkable to see just how striking the effects of coffee were in the group that had the susceptible genetic variant, what we termed “slow caffeine metabolizers” yet no effect whatsoever in those who did not were termed “fast metabolizers”.
Dr. Kim[/caption]
Brian S Kim, MD, MTR
Sol and Clara Kest Professor
Vice Chair of Research | Site Chair, Mount Sinai West and Morningside
Director, Mark Lebwohl Center for Neuroinflammation and Sensation
The Kimberly and Eric J. Waldman Department of Dermatology
Precision Immunology Institute | Friedman Brain Institute
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study?
Response: We generated preliminary data in mice that difelikefalin suppresses itch robustly with very little to no effect on inflammation in a model of atopic dermatitis. This led us to hypothesize that the primary mode of action of difelikefalin must be by direct modulation of sensory neurons to suppress itch and thus would be best suited for a neuropathic itch condition. These are conditions in which itch occurs relatively independently of skin inflammation as in atopic dermatitis due to hyperactive nerves.
Dr. Pierce[/caption]
Karen Pierce, Ph.D.
Professor, Department of Neurosciences, UCSD
Co-Director, Autism Center of Excellence, UCSD
MedicalResearch.com: What is the background for this study?
Response: The mean age of ASD diagnosis and eventual treatment remains at ~52 months in the United States1 - years beyond the disorder’s prenatal origins2, and beyond the age when it can be reliably diagnosed in many cases3.
Currently the only way to determine if a child has autism spectrum disorder (ASD) is to receive a developmental evaluation from an experienced clinician (usually a licensed clinical psychologist). There are often long waiting lists, and only a small number of clinicians have the experience required to make early-age (i.e., between 12-36 months) diagnoses of ASD. Thus, there are many places in the country as well as world wide wherein children wait months or years to receive a formal diagnosis due to a lack of available expertise. Moreover, diagnostic evaluations are expensive and usually cost the parent and/or insurance approximately ~$2,000 or more per evaluation. Finally, clinical evaluations usually take between 2-3 hours to complete and result in fatigue for both the parent and toddler.
Eye-tracking, which generates biologically-relevant, objective, and quantifiable metrics of both visual and auditory preference profiles in babies and toddlers in just minutes, is a technology that can dramatically change how ASD is diagnosed.