The winner of Dec’ PAPER OF THE MONTH is the doctoral student Ben Bar Sade from Prof. Phillipa Melamed lab

23 January 2022

SPOTLIGHT ON RESEARCH
PAPER OF THE MONTH OCTOBER 21

The Committee for Graduate Studies in the Faculty of Biology selects each month the leading scientific article from all the scientific articles published for that month. We are pleased to announce that the winner of this December’s article is the doctoral student Ben Bar Sade from Prof. Melamed lab, whose article was published in BMC biology. On the occasion of the win, we asked Ben to provide us with some interesting details about the study, the path that led to the research, and also a bit about him.

Hi, could you introduce yourself in a few words?
My name is Ben, I was born in the most beautiful place in Israel – Kibbutz Gazit, and in the last several years I’ve been living in Haifa. About 8 years ago, I started my bachelor’s degree here in the faculty and continued to master’s and doctorate studies in the lab of Prof. Philippa Melamed.

Could you explain what Prof. Melamed laboratory is about?
The Melamed lab is working on reproductive endocrinology and epigenetics. We study the hormonal and physiological activity of the mammalian reproductive system and focus on getting a deep understanding of the basic molecular mechanisms that dictate its activity

Could you tell us about your current article/research, what was the main purpose of the research and what did you discover?
The main purpose of the research was to find the molecular mechanisms that mediate the effect of early life adversity on reproductive function. This work is a collaboration with two researchers from England, Prof. Gillian Bentley (Durham University), an anthropologist, and Dr. Reinhard Stöger (University of Nottingham) who studies epigenetic mechanisms. Gillian found that Bangladeshi women whose childhood was in Bangladesh and suffered from a high incidence of intestinal inflammation had later pubertal onset and earlier menopause than Bangladeshi women who migrated to England before the age of 8 years and grew up in a cleaner environment. This suggests that our environment as children has a crucial effect on reproductive function as adults. Reinhard found differences in DNA methylation (an epigenetic mark that can affect gene expression) between these two groups of women. We used a mouse model to investigate the mechanisms involved. Similar to the women who grew up in Bangladesh, mice who suffered from early life intestinal inflammation, had a late puberty onset compared to healthy controls, and their ovarian function was also altered. We identified ~100 genes whose expression changed in the ovaries of mice after inflammation, but the reduction in Srd5a1 gene was striking, due to several reasons:

  1. Srd5a1 was more methylated in the women who grew up in Bangladesh.
  2. Srd5a1 expression has been reported to be lower after various kinds of early life stress, suggesting a broad role in mediating stress effects.
  3. Srd5a1 encodes to the enzyme 5α-reductase-1, which has a central role in the synthesis of steroid hormones in reproductive tissues.
  4.  Srd5a1 expression was lower also in mice hypothalamus – the central control region of reproduction in the brain. We showed that the reduction in Srd5a1 in mouse ovaries correlates with higher methylation levels in an “enhancer” (a genomic region that enhances transcription of a gene). This elevated methylation could lower enhancer activity and thus reduce gene expression. Moreover, we showed that inhibition of the encoded protein, 5α-reductase-1, decreases the synthesis and secretion of GnRH, a central hormone in the regulation of pubertal onset, and delays puberty onset in mice.


The doctoral student Ben Bar Sade from Prof. Melamed lab

  • Can you elaborate on the importance of the discovery? Why will this discovery serve you and what directions does it take? What is the application of the discovery (domains, solutions)? The variability in women’s reproductive lifespan is huge. The end of the reproductive period, characterized by loss of oocytes in the ovaries, is one of the reasons for difficulties of getting pregnant, even at a relatively young age. A deep understanding of all the factors, genetic and environmental, affecting reproductive function, specifically ovarian activity, could help to assess a women’s reproductive status and even predict her fertility capacity in the future, possibly utilizing epigenetic markers. This could help women to make rational choices for planning their future.
  • What drew you to the current lab/project? This project was started as a “research project” in my first degree (a long time ago…). I was fascinated by the opportunity to find molecular explanations for physiological phenomena, which even have social consequences. Of course, the theoretical, technical, and spiritual guidance and support of the people in the lab, especially Philippa and the lab manager Lilach Polinsky, had a crucial role in my decision to stay with this project, in this lab, for such a long time.
  • When you are not “doing” science, what do you do? Playing with food in the kitchen (baking, cooking, eating, and of course sharing it with others), doing sport, hiking, snowboarding at least one week per year (not including Corona time), and occasionally surfing
  • When you grow up who do you want to be? Myself.
  • What are your plans for the future of your career? Would like to believe that using the tools and knowledge that I have earned during my academic years, I could contribute to the fast-growing biotech/pharma industry, in Israel or abroad.

 

A link to the full article: https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-021-01219-6
A link to Melamed lab site: https://mol-endo.net.technion.ac.il/
To Prof. Philippa Melamed page: https://biology.technion.ac.il/en/member/melamed/

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