Reproductive biology and stem cells Lab

Dr. Sangrithi is group leader at the Centre for Stem Cells and Regenerative Medicine at King’s College London

Our research focusses on sex chromosome functions in the germ line, and their role in infertility. We are fascinated to understand how the transcriptional identities of male and female germ cells are established during early embryonic development. Germ cell sexual dimorphism is fixed during genome wide epigenetic reprogramming, stemming from an interplay of cell autonomous and extrinsic cues. Our main goal in the group is to decipher regulatory networks that determine epigenetic states in germ cells, and to use this knowledge in new approaches for cell-based therapy / regenerative medicine. We study sex chromosome effects in germ cells and reproduction, using different model organisms, e.g. mouse, cynomolgus macaque and humans.

Our work is expected to have broader impact not only on sex-chromosome related infertility and aneuploidy syndromes, but also on fertility preservation of germ line stem cells in reproductive medicine, epigenetic inheritance and cancer.

Opportunities to join the lab:

We welcome informal enquiries. Please direct these to Mahesh.sangrithi@kcl.ac.uk

PhDs:

Detailed info for the PhD studentship calls can be found in these links:

Members

Mahesh Sangrithi

Wellcome Trust Clinical Career Development Fellow

Investigating gene regulatory networks in germ cells using multi-modal techniques.

Recent work from our group has identified the activity of gene regulatory networks in spermatogonial stem cells (SSCs), while a number of these map to the X chromosome. The functions of these genes in SSC physiology are poorly understood. We aim to obtain a better understanding of these networks in SSCs using a combination of single-cell transcriptomic and epigenetic profiling methods. Techniques: cell culture, hiPSCs, gene modulation

Effects of X-dosage on germ cell transcriptional identity

We have shown previously that germ cells exhibit unique dosage compensation states, which depend on the number of X chromosomes present. In this project we want to understand how gene expression networks in the germline may be altered by X chromosome dose. Techniques: mouse developmental genetics, FACS, single-cell transcriptomics / CutNTag