Research in the laboratory of Prof. Gil Ast and Prof. Rodad Sharan at Tel Aviv University is trying to understand the epigenetics of autism or why only some of the carriers of the mutation associated with autism are on the autistic spectrum, among other things with the help of theCRISPR. The group won a grant of NIS 4.9 million from the National Science Foundation as part of a personalized medicine program
The National Science Foundation has published the list of winning groups in the second round of grants for the personalized medicine program. In this round, 16 research proposals were selected in the second round of the research program in personalized medicine, which includes unique collaborations between researchers from diverse fields of knowledge and specialization from various health institutions and organizations
The total amount of research grants in the current round of submissions is about NIS 60 million - the total scope of grants for the first two rounds is about NIS 120 million.
One of the groups includes Prof. Gil Ast from the Department of Human Molecular Genetics and Biochemistry at Tel Aviv University and Prof. Rodad Sharan, from the School of Computer Science. The group won a grant of NIS 4.9 million for the purpose of "deciphering the involvement of epigenetic mechanisms in autism and adapting personalized treatment."
The prevalence of carriers of the mutations associated with autism is high - probably ten percent of the population, but not all of them are actually on the spectrum.
Indeed, autism is perhaps the epidemic of the 21st century. In the message given by the team members to the grants committee, they wrote: "Autism spectrum disorders have a clear genetic component, but genetic changes that are highly prevalent in patients are also found in healthy people. We found two genes with high expression in autism, which may be involved in the penetrance of the disorder, because their overexpression in a cellular system causes epigenetic changes in the whole genome, and specifically in genes linked to autism. In the study we will examine cells from sick and healthy subjects who have the same genetic change that characterizes autism and compare them according to epigenetic parameters, splicing patterns and gene expression patterns. Also, a machine learning-based tool for diagnosing autism was developed and a system was developed for changing methylation patterns for personalized treatment. The research was done in collaboration with the Center for Autism Research at Ben Gurion University).
In a conversation with the science website, Prof. Est explains the background to the research: "In the laboratory, we have been investigating the relationship between epigenetics and RNA processing for years. We were the first in the world to show that there is a difference in the form of packaging between sequences that have genetic significance and sequences that have no genetic significance. We started researching the proteins that make up the packaging of DNA called histones. To do this we went ahead and eliminated these genes inside human cells using gene editing technology CRISPR CAS9. We found that eliminating the genes that express the histones affects the RNA processing process."
"One of the researchers in the lab, Yifat Kider, discovered a site in the DNA that is associated with many genetic diseases and genetic traits such as weight. We know that its variants are involved in neurodegenerative diseases. Within this site she found a hundred genes, most of which express the histones."
"We are about to receive samples of autistic patients from a tissue bank in the USA. We specifically chose the type of autistic patients so that we would have different versions of expressions at the same genomic site, and we will also investigate tissues and cell lines of autistics and examine the different expression of epigenetic markers to try to find why autism is on the one hand a genetic disease but on the other hand there are cases where identical twins , who apparently carry the same genetic sequence, one of them is on the autistic spectrum and the other is completely healthy. We hypothesize that the reason for this is that in one of the twins the epigenetic changes occurred in the direction of autism while in the other they did not occur.
Later in the research we will create cell lines on which we will investigate how epigenetics affects the migration of neurons in the brain between a normal person and a person suffering from autism.
"The second and last stage of our research will be dedicated to trying to reach personalized medicine, with the help of Crispr cas9. In this framework, we developed a tool in the laboratory with which we are able to reach any sequence of DNA in the genome and change its epigenetic markers. We have a target sequence that we hypothesize is the key that turns the genes on and off, and in the last step, after we understand the genetic process in depth, try to access it and change its state so that it expresses markers of a normal person. We are collaborating with Prof. Moshe Idan, a doctor who treats people on the autistic spectrum, and among other things, he is supposed to provide us with blood samples from identical twins, one of whom is autistic and the other is not."
What about clinical trials?
"Today it is still not possible to use CRISPR CAS9 for clinical trials, but I estimate that when we understand the epigenetic pathways related to autism, probably in four years, there is a high probability that this use will already be possible."
Autism and schizophrenia are visual diseases
According to Prof. Est, there is a connection between autism and schizophrenia. In the condition of autism, there are certain genes that express the histones so that their expression level increases, and in schizophrenia the expression level of those genes decreases. We believe that these are sister diseases that are mirror images of each other. What happens more in autism happens exactly the opposite in schizophrenia. Therefore, from our research on epigenetic pathways in autism, we will be able to develop computational tools such as machine learning to understand how the same site within the DNA that is linked to many genetic diseases and genetic traits is involved in different diseases, something that will advance the finding of treatment methods that are individually adapted to each of the diseases.
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Hello to all readers,
I saw something in one of the comments that I also wanted to write.
The word "disease" is repeated over and over again.
People with autism are not a disease.
Autism is a syndrome
You are taking us all back decades when you call someone who is not on the autism spectrum "healthy". Autism is not a disease.
In my opinion....epigenetic effects should be examined in a wider spectrum. It is possible that autism erupts due to environmental reasons during the critical phase of the first year for a newborn when the communication systems are taking shape and then an external disturbance enters that disrupts their operation.