[1] After earning his Ph.D, he stayed and worked under circadian biologist Dr. Michael Menaker at the University of Virginia where he most notably helped discover the tau mutation in golden hamsters.
While working as a grad student under Dr. Michael Menaker, one of the modern grandfathers of circadian biology, he discovered a golden hamster that had a period noticeably less than 24 hours.
[5] He later worked with a team of circadian biologists led by Dr. Joseph Takahashi to identify the location of the mutation responsible for tau mutant hamster's 20 hour period.
One of the first uses of the mutant (tau) golden hamster was the identification of the suprachiasmatic nucleus (SCN) as an important pacemaker of locomotive daily rhythms.
For example, having a pulse of light during a diurnal animal’s rest phase could lead to a change in period and rhythmicity, even for some time after the short stimulus.
[10] In his work done with Dr. Gary Pickard in the Menaker lab, Dr. Ralph studied mice which had their intergeniculate leaflet (IGL), a retinal pathway important for perceiving light, surgically removed.
Transplanting fetal brain grafts with SCN reversed the decline in behavioral rhythmicity naturally associated with age and extended longevity by 20% in adult hamsters.
These findings suggest that clock speed slows down with age and decreased behavioral rhythms (measured as running time) are highly predictive of lifespan within a few weeks.
[17] A recent meta-analysis (2022) of neural transplantation studies showed that replacing dopamine-producing cells with stem-cell derived equivalents is not only safe for patients but can improve motor function and daily living ability.
[18] Another study similar to Dr. Ralph’s work includes work done in 2014 which showed that transplantation of interneurons led to the restoration of memory and cognitive function in an Alzheimer’s disease mouse model In particular, the transplantation of inhibitory interneurons shed light on the role inhibition plays in generating normal function through interplay with excitatory neurons.
[19] Ralph continued his interest in circadian research at the University of Toronto, specifically in smaller mammalian models of mice and hamsters.
They observed that implicit time-memory, an unconscious memory of a specific time that can be anticipated during which a significant event repeatedly occurs, modulates PER2 mRNA expression only in the striatum of the brain and without affecting the overall circadian clock.