Rachel A Jesudasan - Session 01, 2023-04-19

(00:00:35) Childhood in Kottarakara and moving to Rishi Valley Rachel studied till Class 7 in Malayalam medium school in Kottarakkara. She qualified for a scholarship for entry into public residential schools in 1969. While being admitted into Rishi Valley School, there was concern by the school principal about her coping with English-medium classes, was made to repeat some classes. Rachel talks about her own self-confidence owing to her training by her father using books to learn English.

(00:08:00) Experience in Rishi Valley The year she joined, there was a lot of excitement of witnessing the first man on the moon. She speaks about her classmate Bob Balaram who would go on to become a NASA scientist. Early academic interests. She speaks on the habit of reading and being inspired by biographies. She describes the life and non-academic activities at Rishi Valley – sports, music, dance. Memories of boys playing cricket on Sunday, sitting under the neem tree. The daily 5 minutes of silence at sunset left an impression on her.

(00:17:29) Choosing what to do after school Early goal of becoming a doctor and helping the poor. She talks of her deep dislike for history and debates with history teacher. Memories of science club and being influenced to apply for NCERT's science talent (NST) exam. Doing a project on electrochemical series for the exam. Anxiety over preparing for the exam, father's support, and eventually qualifying. [Archivist’s note: 22:30 to 26:43 - Connection issues] Personal and technical reasons for opting for Women's College in Trivandrum over Physics at IIT Delhi and BITS Pilani.

(00:32:29) UG and PG experience and summer schools She describes the biology training she received in NST's Annual summer schools at different institutes. The impact these summer schools left on her, how it was different from usual classrooms. Memory of getting to ask Prof Maheshwari a doubt and being encouraged by the response. Reflections on why these summer schools were so effective – the students were the cream of the country. The college not being particularly exciting to her, her desire to leave Women's college after BSc but being advised to stay back.

(00:38:13) After Masters She wrote to Prof Mercy Jacob at BHU and was invited to join. She describes the support from father & mother. She joined Prof. Tikaram Sharma and started work on sister chromatid exchange, a field that was completely new to her.

(00:41:57) Work culture at BHU lab Memories of the first six months, the freedom she received from her guide to use all her time to read and learn techniques. Teatime discussions between researchers and four PIs of the cytogenetics unit. Facing many failures in experiments and briefly thinking about quitting, before a pep-talk by Pradeep Sinha made her decide to stay back.

(00:44:49) Nature of scientific work She describes the concept of sister chromatid exchange (SCE). There was much intrigue around this phenomenon and its mechanism. The difficulty of the cells not growing in the tissue culture during attempts to observe SCEs. About how she went about her attempts to localise SCEs precisely on chromosomes. She describes the technique she standardised called harlequin banding. She describes the system she worked on, muntjac chromosomes. Submitting in 1988 and receiving degree in 1989. [Archivist’s note: 52:13 to 57:09 - Connection issues]

(00:57:37) Early years in CCMB Getting into CCMB in 1986 after her guide left BHU for sabbatical and her fellowship ran out. Completing thesis work over summer breaks. She joined as scientist-B, recruited by PMB for Lalji's group (Lalji would join later). Lalji was once a member of the same lab in BHU, but Rachel had only met him once. She was part of the team setting up the lab – she described what this involved. She recalls early experiments she did – one of these is actually her latest paper.

(01:01:40) Research into sex chromosomes She talks about the first study started in CCMB which finally got published in 2022 "Single-cell variations in the expression of codominant alleles A and B on RBC of AB blood group individuals". She describes why this study was particularly satisfying to her – how it has to do with classical concepts in biology. How her work challenged the dogma that classical codominant alleles and autosomal homologs are functionally similar. She recalls going for a conference in Cold Spring Harbor and interaction with Amar Klar. She summarises Klar's discovery of a yeast mating type switching mechanism. At the conference, Klar seemed impressed by Rachel's work.

(01:08:07) CCMB's early years and evolution While acknowledging that the founders were visionaries, Rachel also notes problems with their ideas of how the institute would be structured. Lalji was brought from Edinburgh to develop the ideas, and Rachel was one of those hired to be part of his team. She describes the negatives of the group leader-junior scientist model – lack of independence for junior scientists. She briefly mentions that many of them fought their way to get some independence. CSIR's removal of Scientist-B recruitment, after realising the problems of this model. Despite all this, she describes how she was at the right place (Lalji's lab) at right time (around this time in 1990, the discovery of sex-determining gene was announced). [Interlude 1:12:41-1:13:15 clarification about Drosophila X-chromosomes] .

(01:13:25) Working under Lalji The difference between sex determination in mammals (homogametic female) vs snakes/birds (homogametic male). She notes that her memory on some details might be faulty. She describes how she was able to use Lalji's heterochromatic probes for her work to find that Y-heterochromatin derived RNAs regulate coding genes on autosomes. She explains why this is significant, and how this challenges, existing ideas of Y as a genetically isolated chromosome. It was published in 2007 as 'Novel noncoding RNA from human Y distal heterochromatic block (Yq12) generates testis-specific chimeric CDC2L2' in Genome Research. This was breakthrough work and it received emphatic validation from MRS Rao.

(01:19:52) Impacts of Y chromosome research She never cared about doing "risky" science and she explains why. She acknowledges the difficulties in publishing such results, especially when it was coming from India. She elaborates on the stereotypical comments that come after quality work emerges from Indian scientists. She shares thoughts on how she was fortunate to publish in the journal Genome Research, and how it may have worked in her favour that the editor's spouse was an expert in the area. An instance when this novel research came up in Parliament to show that India was active in human genome research. She said that there is persisting interest in this topic. She goes on to study heterochromatin in mice and found similar results in mouse Y-chromosome, but using another mechanism ('Y chromosomal noncoding RNAs regulate autosomal gene expression via piRNAs in mouse testis'). She was called for many conferences because of this work – her use of genomics and proteomics generated a lot of interest.

(01:29:28) Thoughts about sex chromosomes and future work There is more to mammalian Y than being male-determining chromosome, but it definitely has the sex determination region. Recent development where she and an international group of scientists have put up a letter of interest for a Human Frontier Science Programme project. Her belief that now that interest in this field is established, the work will continue. She describes some studies that further establish that Y-chromosome has more functions. For example, a study showing Y-deleted animals show stress-related behaviour. Her hopefulness for the planned future work.

(01:37:49) Post-retirement life The case of Osmania University (her current affiliation) not being recognised for the HFSP grant application, and the possibility of joining there as adjunct professor discussed by the University. She still has some papers left to publish – one is about the two strands of DNA and the distinct functions they disseminate to the two daughter cells during division.

(01:39:44) Her work ethic and challenging ideas of 'productivity' She comments on having no long-term collaborators. Swimming against the current and the cost of doing that. Her ideas about publishing less frequently, but focusing on publishing 'full stories' and high impact. She brings up the example of two of her papers that took around 20 years to publish. Working on heterochromatin and non-coding RNAs at a time when it was not very mainstream. She is very fulfilled after making multiple fundamental discoveries.

(01:45:16) Technology advances is not enough She describes nanopore sequencers like MinION device and how they can help genomic research. She comments that while technology and technical knowhow has advanced, biological questions are still lagging. DNA is the easy part, but what does it mean? – that is what her work focused on. She describes Lakhotia and others' concern about biotechnology emerging as a course. [01:49:48 Aside: One question that remains is why do species-specific sequences of noncoding RNA evolve? It might be related to reproduction, a species-specific event.]

(01:51:53) Altruistic activities She narrates the success story of an underprivileged boy who she supports. She describes how she interacts with children, many orphans, and generally spends time with them. She also talks about helping build a house for a daily wage worker at CCMB.