Dr. Anusree Lakshmi Sivadas
Postdoctoral Researcher
Stuttgart
Summary
Curious and hardworking Postdoctoral researcher trying to unravel the mystery behind cancer progression and metastasis with a strong backing of molecular biology. I studied the molecular mechanisms underlying nuclear RNA- surveillance during my PhD and transitioned into cancer research for my first Postdoctoral position. Currently, using my expertise in molecular biology to understand the intricacies of Pancreatic ductal adenocarcinoma.
Overview
11
11
years of professional experience
Work History
Postdoctoral Research
RBCT- Robert Bosch Center For Tumor Diseases
06.2022 - Current
- Under the guidance of Professor Steven Johnsen
- Project background: Identifying the various molecular and epigenetic factors that contribute to subtype identity in Pancreatic ductal adenocarcinoma (PDAC).
- Two major molecular subtypes, “basal” and “classical” have been identified in PDAC. This PDAC subtype identity is determined by master transcription factors (MTF) such as ΔNp63 and GATA6. Additionally, studies have identified subtype-specific enhancer regions characterized by enhancer RNA (eRNA) production, associated with more frequent chromatin interactions and subtype-specific gene activation. However, how these eRNAs and/or eRNA-mediated interactions contribute to subtype identity remains largely unknown and forms the crux of my project.
- By employing a combination of high-throughput sequencing techniques and analyses, I identified that the 3’ endonucleolytic subunit of the integrator complex (INTS11) contributes to the subtype-specific identity in PDAC. Ongoing analysis is expected to shed more light on the molecular mechanisms and complex interactions underlying the role of INTS11 in regulating the PDAC subtype identity.
- Manuscript under preparation.
PhD- Genome Sciences
JCSMR- John Curtin School Of Medical Research
10.2017 - 07.2023
- Under the guidance of Associate Professor Tamas Fischer
- Project entitled: Studying MTREC complex and its role in nuclear RNA surveillance.
- In S. pombe , the 11-subunit MTREC complex is responsible for detecting classes of pervasive transcripts and aberrant mRNAs and targeting them to the nuclear exosome for degradation. However, the mechanism by which the MTREC complex is recruited to different classes of pervasive transcripts remained elusive. In my study, I primarily concentrated on two of the most intriguing subunit proteins of the MTREC complex, the helicase Mtl1 and poly(A) polymerase Pla1. Our study revealed that while the entire MTREC complex is not essential for cell survival, a “truncated” MTREC complex without Mtl1 helicase is lethal for the cells. My work on the Pla1 subunit revealed that Pla1, as part of the MTREC complex, hyper-adenylates classes of pervasive transcripts for their efficient degradation while also playing roles in the efficient assembly of facultative heterochromatic islands.
- Employed high-throughput sequencing techniques (RNA seq, ChIP seq, Nanopore sequencing) to study the transcriptome. Proficient in studying protein-protein interactions using techniques such as TAP-purification followed by mass-spectrometry and co-IP.
- Two successful publications.
Final year Masters project
CCMB - Centre For Cellular And Molecular Biology
11.2016 - 04.2017
- Under the guidance of Emeritus scientist Purnima Bhargava
- Project entitled: Role of H2A.Z in nucleosome stability around tRNA genes in Saccharomyces cerevisiae.
- Nucleosomes are composed of a variety of histone proteins and sometimes their variants. H2AZ is a variant of H2A and my work demonstrated that the instability of nucleosomes on tDNA loci may be attributed to the presence of H2AZ in these nucleosomes. Deletion of H2AZ resulted in more stable nucleosomes, while presence of the same in the nucleosomes around tDNA made them easily dissociable.
Summer fellow
IISER - Indian Institute Of Science Education And Research
05.2016 - 07.2016
- Under the guidance of Dr. N.G Prasad
- Project entitled: Studying Lytic activity by turbidity assay in Drosophila melanogaster.
- Lytic activity checks the immune marker enzyme Lyzosyme produced as a result of bacterial attack. My work showed the presence of lytic activity in the extracted haemolymph of adult Drosophila flies and that it helps flies combat bacterial infections.
INSA NASI Fellow
CCMB - Centre For Cellular And Molecular Biology
05.2015 - 07.2015
- Under the guidance of Emeritus scientist Purnima Bhargava
- Project entitled: The effect of Methylmethanesulphonate (MMS) on yeast transcription factor III C (TFIIIC).
- TFIIIC is a key transcription factor for RNA Pol III and has six (Tfc1, Tfc3, Tfc4, Tfc6, Tfc7, Tfc8) subunits. Through our work, we could demonstrate that Tfc3 and Tfc1 mutants were not sensitive towards MMS at low concentrations. At the same time, Tfc3 mutants were more sensitive to the increases in MMS concentration compared to Tfc1 and other RNA pol III mutants that were studied.
Summer trainee
DRDO-DIPAS- Defense Institute Of Physiology And Allied Sciences
05.2013 - 06.2013
- Hands-on training in handling mice, surgical operations including intravenous and intra peritoneal injections.
- Quantitative and qualitative estimation of urea, carbohydrates, lactate and cholesterol
Education
Ph.D. - Genome Sciences
JCSMR, ANU- Australian National University
Canberra, Australia07.2023
Integrated MSc - Lifesciences
CUTN - Central University of Tamil Nadu
Tamil Nadu, India04.2017
Higher Secondary Education -
GVHSS, Mananthavady
Kerala, India03.2012
Skills
Project handling/leading, independent as well as in a team
Highly collaborative
Excellent scientific communication
Experienced and proficient in human cell line/ yeast cell/ Ecoli/ Drosophila maintenance and experiments
Expert in various high throughput sequencing and analyses
Publications
- The zinc-finger protein Red1 orchestrates MTREC submodules and binds the Mtl1 helicase arch domain, Nature Communications, 12, 3456, 2021
- Mechanistic insights into RNA surveillance by the canonical poly(A) polymerase Pla1 of the MTREC complex, Nature Communications, 14, 772, 2023
Scientific skills
- RNA/DNA studies : Basic RNA/DNA isolation, PCR, RNA/DNAlibrary preparation followed by sequencing (seq.).RT-PCR, Chromatin-IP (ChIP) followed by q-PCR/seq., RNA-IP (RIP) followed by library preparation and seq. (Illumina, Oxford-Nanopore Direct RNA seq.), CRosslinking and Analysis of cDNA (CRAC).
- Protein studies: TAP-purification followed by Mass Spectrometry (MS) and analysis, Immunoprecipitation (IP), Co-IP and Western blot.
- Yeast genetic manipulation: Tetrad dissection, tagging and deletion of genes, sensitivity assays, basic plating and growing techniques.
- Drosophila studies: Handling and maintenance, ELISA- Enzyme Linked Immunosorbent Assay and Immunologic techniques.
- Acquainted with basic Molecular, Biochemical, Immunological and computational techniques (basic RNA-seq, ChiP seq analyses using Galaxy)
- Experienced in maintaining and handling human cell lines.
Accomplishments
- Lightning talk (3 minutes) and poster presentation at EMBL Australia Postgraduate Symposium 2021- EAPS 2021.
- Panelist in the Central University of Tamil Nadu Alumni Association (CUTNAA) organized virtual panel discussion on “Opportunities abroad for higher education” held on 18th December 2021.
- Panelist in the Student IQAC organized National Webinar on “Selective degradation of genetic materials” held on 29th September 2020.
- Attended: 40th Annual Lorne Genome Conference 2019, Cumberland Lorne Resort, Victoria.
- Lightning talk (3 minutes) and poster presentation at 6th EMBL Australia PhD course held at The University of Tasmania, Hobart, Australia, 2019 (June 24- July 5).
- Attended "From Ensembles to Single-Molecule Analysis - Modern Methods of RNP Analysis 2018", Regensburg, Germany.
- Participated in 3-day workshop on ‘Emerging Trends in Chemical Sciences’ (September 21-23, 2012) organized by Department of Chemistry, Central University of Tamil Nadu.
- Attended International conference CANCERCON – 2014, held at IIT Madras from 30th-2nd Feb 2014
- Attended National conference on ‘Advances in modern biology and environment’ organized by Department of Zoology of H H Rajah’s Government College, Pudukottai, Tamil Nadu.
- Participated in National Conference on ‘Recent trends and future advances in Life Sciences’ (RFTALS) held at Central University of Tamil Nadu, India
- Participated in a National conference at St. Joseph College, Trichy on ‘Prospects and challenges in stem cell research’.
References
- Prof. Steven A. Johnsen, PhD, Scientific director, Robert Bosch Center for Tumor Diseases, Forschungsexzellenz des Bosch Health Campus, Auerbachstr. 112, 70376, Stuttgart, Germany, +49 711 8101-3693, steven.johnsen@bosch-health-campus.com
- A/Prof. Tamas Fischer, Associate Professor, Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, Building 131, Garran Road, Canberra, ACT, 2601, Australia, +61261252194, tamas.fischer@anu.edu.au
- Prof. Thomas Preiss, Professor/ Division Head, Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, Building 131, Garran Road, Canberra, ACT, 2601, Australia, thomas.preiss@anu.edu.au
- Emeritus Scientist Purnima Bhargava, Emeritus Scientist, CSIR-Center for Cellular and Molecular Biology, Hyderabad, Telangana, 500007, India, 040-27192603, purnima@ccmb.res.in
- Dr. Rippei Hayashi, Group Leader, Division of Genome Sciences and Cancer, The John Curtin School of Medical Research, Building 131, Garran Road, Canberra, ACT, 2601, Australia, rippei.hayashi@anu.edu.au
Timeline
Postdoctoral Research
RBCT- Robert Bosch Center For Tumor Diseases
06.2022 - Current
PhD- Genome Sciences
JCSMR- John Curtin School Of Medical Research
10.2017 - 07.2023
Final year Masters project
CCMB - Centre For Cellular And Molecular Biology
11.2016 - 04.2017
Summer fellow
IISER - Indian Institute Of Science Education And Research
05.2016 - 07.2016
INSA NASI Fellow
CCMB - Centre For Cellular And Molecular Biology
05.2015 - 07.2015
Summer trainee
DRDO-DIPAS- Defense Institute Of Physiology And Allied Sciences
05.2013 - 06.2013
Ph.D. - Genome Sciences
JCSMR, ANU- Australian National University
Integrated MSc - Lifesciences
CUTN - Central University of Tamil Nadu
Higher Secondary Education -
GVHSS, Mananthavady