Dr Sovan Sarkar

Supervisor Details

Contact Details

Department of Cancer and Genomic Sciences, University of Birmingham

Scientific Background

Research Interests

Our lab is interested in a biological process called autophagy, which is utilized by the cells to perform house-keeping function at basal level or to eliminate toxic materials during stress conditions. Autophagy is an intracellular degradation process for the removal of unwanted macromolecules, damaged organelles and invading pathogens from the cells. During starvation, it also recycles bulk cytoplasmic components to provide inputs to cellular metabolism for generating energy and building new proteins.

Cells engulf autophagic cargo inside double-membrane vesicles called autophagosomes that are formed from isolation membranes called phagophores. Autophagosomes then fuse with the lysosomes to form the degradative autolysosomes where the cargo is degraded by the lysosomal enzymes. This dynamic process encompassing fusion of vesicular compartments and degradation of cargo is referred to as autophagic flux. Autophagy is classically regulated by the mechanistic target of rapamycin (mTOR) pathway but can be also controlled by mTOR-independent pathways; both avenues being anemable to chemical perturbations. The role of autophagy in the selective clearance of undesirable materials for replacing old cellular components or to combat stress situations, as well as the bulk degradation of cytoplasmic materials during starvation for energy generation is vital for ensuring cellular and energy homeostasis. This homeostatic function of autophagy is essential for cell survival, organ function and human health. Deregulation of this process leads to accumulation of deleterious autophagic cargo that is harmful to the cells. Dysfunction in autophagy occurs in myriad human diseases where it is implicated in the disease pathology whereas therapeutic modulation of autophagy with small molecules is beneficial in certain contexts.

We are utilizing human embryonic stem cells (hESCs) and disease-specific induced pluripotent stem cells (iPSCs) to establish physiological and disease-relevant human cellular platforms for investigating the role, regulation and therapeutic manipulation of autophagy in a manner relevant for human biology. We are differentiating these human pluripotent stem cells into neural precursors, neurons, monocytic cells, macrophages and fibroblasts using established protocols for studying autophagy.

Scientific Inspiration

Prof. Rudolf Jaenisch, my postdoc mentor at Whitehead Institute in MIT, who is instrumental advancing the human stem cell field. He is a visionary and an outstanding leader. He has trained and supported several of his lab members to become world experts in various research areas.

Research Groups

Sovan Sarkar Lab

Supervision Style

In three words or phrases: outcome-oriented, student-centred, collaborative.

Provision of Training

I will take responsibility for your initial technical training, which will be supervised predominantly by my experienced post docs/PhD students and myself, and thereafter you will gain more independence and freedom to operate.

Progression Monitoring and Management

Initially, I like to be kept up to date on a daily basis and will expect to see evidence of work progress/data generation on a weekly basis, and after you gain basic work independence, I will set out project goals and my expectations of your progression as well as discuss action plans on a weekly basis. I will oversee that you unlock your full potential to attain maximal success.

Communication

I am approachable and known to email my team at all hours of the day and night, however I will not expect you to do the same; and also my team has a WhatsApp group chat with which we regularly communicate during the week and weekends. I am happy to discuss any issues that are impacting your ability to fulfil your potential or my/our expectations.

PhD Students can expect scheduled meetings with me:

In a group meeting

At least once per week

In year 1 of PhD study

At least once per week

In year 2 of PhD study

At least once per week

In year 3 of PhD study

At least once per week

These meetings will mainly be face to face. I am usually contactable for an instant response every working day.

Work Patterns

Certain tasks in my lab need to occur at set times, and students need to be able to commit to a rota/timetable shared with other members of the team.

Notice Period for Feedback

I need at least 1 week’s notice to provide feedback on written work of up to 5000 words.

MIBTP Project Details

Current Projects (2025-26)

Primary supervisor for:

Investigating the homeostatic landscape of autophagy in cell survival using human pluripotent stem cell-derived neuronal and cerebral organoid platforms

See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.

Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).

Investigating the homeostatic landscape of autophagy in cell survival using human pluripotent stem cell-derived neuronal and cerebral organoid platforms

Secondary Supervisor(s): Professor Timothy Barrett

University of Registration: University of Birmingham

BBSRC Research Themes: Integrated Understanding of Health (Ageing)

Project Outline

One of the commonly deregulated cellular processes in ageing and neurodegeneration is autophagy. It is involved in the removal of undesirable macromolecules (like protein aggregates) and damaged organelles (like mitochondria) from the cells, thereby acting as a vital homeostatic pathway pertinent for cellular survival and human health. Conversely, malfunction of autophagy is harmful to the cells, particularly for post-mitotic neurons causing neuronal cell death [1]. We recently described an evolutionarily conserved role of autophagy in promoting cell survival by maintaining the levels of a metabolite called nicotinamide adenine dinucleotide (NAD), whereas loss of autophagy compromises cell viability via depletion of NAD [2–4]. However, the mechanistic landscape underlying the causal link between dysfunctional autophagy and cytotoxicity is not fully understood. To undertake basic research in a manner relevant to human biology, we are harnessing the power of human embryonic stem cells (hESCs) for differentiating into isogenic human cell types and organoids, and have employed genome editing technologies to establish autophagy knockout genetic models [2].

Question

This project addresses a core question in the field of autophagy – How malfunction of autophagy in age-related neurodegeneration mediates neuronal cell death and degeneration of the brain?

Experimental platform

We will utilize our hESC model of autophagy deficiency for differentiating into isogenic human cortical neurons (2D cultures) and cerebral organoids (3D min-brains) that exhibit increased cell death.

Aims

To understand the homeostatic role of autophagy in neuronal survival and brain health, we aim to identify the perturbations in biological pathways and metabolic processes mediating cell death underlying autophagy deficiency.

Methodology

In this project, we will utilize wild-type and autophagy knockout hESC lines to generate cortical neurons and cerebral organoids. To underpin the cytotoxic mechanisms underlying autophagy deficiency, we will undertake unbiased multi-omics analyses using existing UoB facilities and established external collaborations. We will perform metabolomics, transcriptomics, and proteomics analyses to identify global changes in metabolites, gene expression and protein levels at cellular level arising due to loss of autophagy. We have recently carried out these methodologies coupled with computational approaches for studying the role of autophagy in cellular and metabolic homeostasis in hESCs. We will initially focus on cortical neurons and then on cerebral organoids to identify a common signature of cellular perturbations. Key changes will be confirmed by biochemical and cell biology techniques, and emphasis will be given to energetic deficits arising due to stress-related pathways or accumulation of autophagy substrates. Finally, key findings will be confirmed in patient iPSC-derived cortical neurons and cerebral organoids of two rare neurodegenerative diseases associated with defective autophagy that we are currently utilising for biomedical studies.

Outcome

Gaining fundamental insights of the cytotoxic mechanisms underlying loss of autophagy will not only contribute to the basic understanding of the homeostatic role of autophagy in cell survival but will also have the potential for biomedical exploitation in age-related neurodegeneration. Moreover, this work could reveal novel autophagy substrates in the neuronal system. The outcome of this project will thus be of basic and biomedical relevance, along with multiple publications and possible patent applications.

References

[1] Seranova et al. Journal of Molecular Biology, 432: 2754, 2020 (PMID: 32044344);

[2] Sun et al. Cell Reports, 42: 112372, 2023 (PMID: 37086404);

[3] Kataura et al. Developmental Cell, 57: 2584, 2022 (PMID: 36413951);

[4] Wilson et al. Trends in Cell Biology, 33: 788, 2023 (PMID: 36878731).