Partha Das Lab research

Collaborations | Student research projects | Publications

About Dr Partha Das

Education

1. PhD, Molecular and Developmental Biology, Summa cum laude, Wellcome Trust/ Cancer Research UK Gurdon Institute, University of Cambridge, UK; and University of Gottingen, Germany (2009)
2. MSc, Molecular Biology, International Max Planck Research School For Molecular Biology, Gottingen & University of Gottingen, Germany (2004)
3. MSc, Zoology and Molecular Biology, Department of Zoology, University of Pune, India (2002)

Research experience chronology

1. Post-doctoral Research Fellow, Supervisor: Stuart Orkin, MD, Boston Children’s Hospital/Dana Farber Cancer Center, Harvard Medical School, Boston, MA, USA (March 2010-December 2016)
2. Graduate student, Supervisor: Eric Miska, PhD, Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK (April 2005-July 2009)
3. Research student, Supervisor: Ludger Hengst, PhD, Max Planck Institute For Biochemistry, Martinsried, Germany (September 2003-March 2005)
4. Research student, Supervisor: Dileep Deobagkar, PhD, Department of Zoology, University of Pune, India (June 2001-July 2002)

Honours & Accolades

• NHMRC Project Grants (2019-2022)
• London Law Trust Medal Fellowship at King’s College London (2016-2018) to start up the independent lab
• Cancer Research UK (2005-2009)
• Max Planck Research fellowships (2003 Sep-2005 Mar)
• Max Planck Research fellowships (Sep 2002-Aug 2003) during the study of MSc

Our research

Research themes and current projects

1. Epigenetics
2. Epitranscriptomics
3. Embryonic stem cells and cortical organoids, for neurodevelopmental disorders

1. Epigenetics

Epigenetic modifications (DNA and histone modifications) are highly dynamic and regulate gene expression patterns during maintenance of cellular state, differentiation and development and in response to environmental signals. Epigenetic modifications are constantly reshaping the chromatin architecture, 3D structure and accessibility of genes to the transcription machinery for gene expression (Figure 1). We are interested in exploring how gene expression programs are regulated in order to control embryonic stem cell (ESC) state, differentiation and development; and how deregulation of gene expression programs cause diseases.

Ongoing and future projects in our lab include:

1. Dissecting the combinatorial functions of histone demethylases in transcriptional regulatory networks in mouse ESCs (mESCs)
2. Identifying novel epigenetic regulators using CRISPR-Cas9 mediated functional genetic screen and investigating their precise functions in mESCs
3. Examining the detailed functions of Enhancer and Super-enhancer regulatory elements in mESCs
4. Understanding the roles of 3D genome organization in transcription regulation
5. Investigating the epigenetic dynamics in normally developing brain and in neurodevelopmental disorders using the mouse and human brain organoids

^{Figure 1. The schematic diagram represents how histone modifications, DNA methylation, non-coding RNAs and regulatory elements 
maintain 3D genome organization and regulate gene expression. (Courtesy- PPD lab).}

2. Epitranscriptomics or RNA epigenetics

Eukaryotic RNAs carry more than 150 distinct chemical modifications, some having been demonstrated as being reversible. The understanding of each of these RNA modifications is incomplete and just beginning to emerge. The majority of the RNA modifications have been characterised in non-coding RNAs, including transfer RNAs, ribosomal RNAs, small nuclear RNAs and, to some extent, messenger RNAs. Advancement of next-generation sequencing tools has empowered the identification of several distinct internal RNA modifications on a transcriptome-wide scale, including 6-methyladenosine (m6A), 1-methyladenosine, pseudouridine (Ψ) and 5-methylcytosine (m5C)— these are the four most commonly occurring and extensively investigated RNA modifications to date (Figure 2). Recent studies have begun to elucidate the molecular and biological functions of these internal RNA modifications in many organisms, from yeast to mammals. Several RNA modifications have already been linked to human diseases, including cancer, cardiovascular disease, neurological disorders, metabolic disease, mitochondrial-related defects and genetic birth defects. We are interested in learning how these RNA modifications can regulate genetic information at the transcriptional, post-transcriptional and translational levels in the context of ESC state maintenance, development and diseases.

Ongoing and future projects in our lab include:

1. Investigating the role of RNA modifications in ESCs and other differentiated cell types
2. Identifying new factors (Writes, Erasers, and Readers) in m6A pathways and studying their detailed mechanism of action in m6A RNA modification and gene regulation in ESCs
3. Dissecting the role of RNA modifications in normally developing brain and in neurodevelopmental disorders using brain organoids
4. Understanding the role of RNA modifications in cancer

^{Figure 2. Most abundant internal chemical modifications in mRNAs; and their distribution. (Courtesy- PPD lab).}

3. 3D brain organoids to investigate normal neurodevelopment and neurodevelopmental disorders (NDDs)

Three-dimensional (3D) brain organoids derived from embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), appear to resemble many aspects of spatial organization and functionality of the developing brain. Brain organoids or cerebral organoids reflecting the broad regional identities. Alternatively, they may contain structures that resemble specific brain regions, therefore can be referred to as organoids of that regions– such as forebrain organoids, midbrain organoids etc. Recent advancement of the brain organoid generation from ESCs/iPSCs (or patient-derived iPSCs) provide a new tool to model both “normal” and “pathological” human brains, and that eventually enhance our ability to study human brain biology and diseases. Currently, we are using brain organoids to study the roles of epigenetics and epitranscriptomics in normal neurodevelopment and neurodevelopmental disorders (NDDs), as well as in neurological disease modelling. Besides, we are also using CRISPR-Cas9 genome editing tools to manipulate genes/genome in ESCs and iPSCs (or patient-derived iPSCs) to check their effect in the brain organoids. This will be immensely important for studying neurodevelopment, NDDs, disease modelling and personalized medicine.

^{Figure 3. Immunostaining of an entire mouse cortical organoid represent cortical markers Pax6 (neural progenitors),
Tuj1 (neurons) on day 10 (A). Pax6+ (neural progenitors), Tuj1+ (neurons) rosettes on day 10 (B). (Unpublished, PPD lab).}

^{Figure 4. 3D imaging of Pax6+ (neural progenitors, green), Tuj1+ (neurons, red) rosettes from human cerebral
organoid on day 40 (B). (Unpublished, PPD lab).}

Research activities

Major research interests are:

• Epigenetics
• Epitranscriptomics
• Regulatory elements
• 3D genome organization
• Genome and epitranscriptome editing
• Embryonic stem cells
• Cortical organoids/mini brains (human and mouse)
• Neurodevelopmental disorders
• Neuroscience
• Cancer
• Computational biology

Techniques/expertise

• Cell and Molecular Biology
• Biochemistry
• CRISPRs
• CRISPR screens (using sgRNAs to target all the genes in the genome, epigenetic regulators and regulatory elements)
• NGS (ChIP-seq, ATAC-seq, Hi-C, RNA-seq, m⁶A RNA-seq, m⁵C RNA-seq, Ribo-seq, PRO-seq), Proteomics
• Bioinformatics
• Computational biology

Disease models

Neurodevelopmental disorders

Collaborations

We collaborate with many scientists and research organisations around the world. Some of our more significant national and international collaborators are listed below. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).

International collaborators:

Professor Stuart Orkin (Harvard)
Professor Eric Miska (Cambridge)
Dr Effie Apostolou (Cornell)
Dr David Hendrix (Oregon)
Dr Leighton Core (Connecticut)
Dr Dan Bauer (Harvard)
Dr Luca Pinello (Harvard)
Professor Jonghwan Kim (UT Austin)
Dr Wee Wei Tee (Singapore)
Dr Jonathan Loh (Singapore)
Professor Giuseppe Testa (Italy)

National collaborators:

Professor José Polo (Monash)
Dr Lee Wong (Monash)
Professor Stephen Turner (Monash)
Associate Professor Chen Davidovich (Monash)
Dr Ralf Schittenhelm (Monash)
Professor Ian Smyth (Monash)
Associate Professor Craig Smith (Monash)
Professor Ryan Lister (UWA)
Lev Kats (Peter Mac)
Luciano Martelotto (University of Melbourne)
Nathan Palpant (UQ)

Student research projects

The Partha Das Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short-term research opportunities available. You are encouraged to contact Dr Partha Das regarding potential projects that align with the presented research themes.