At conception, we all inherit a fortune. Six billion base-pairs worth of instructions for how to produce each and every specific component and emerging properties of our cells, body-plan, physiology, mind, and more.
These legacy instructions are the software needed to program the matter we consist of, and they are literally ancient. However, while much of our programming was optimized already a billion years ago, other components has only recently been introduced into our genomes.
The quest to adapt to changing environments and conquer ecological niches demands that all organisms include a certain level of creative destruction, so that fitting changes are inherited in the offspring through trial-and-error.
As with any large and comprehensive set of instructions, our genome therefore contains conflicting, ambiguous, repurposed, obsolete, inflated, suboptimal, and even selfish components.
Every genome therefore has to contain and uphold a range of conflicts of interests and trade-offs, and much of the collective action of DNA-bound factors and epigenetic modifications conceivably serve to ensure a coordinated and appropriate use of the genome.
Our overarching passion is to seek understanding of how inbuilt genomic conflicts of interests are handled by mammalian organisms.
A key interest is to understand the remarkable environment existing when the mammalian oocyte is fertilized and become an embryo. During this process, extensive genomic reprogramming happens, epigenetic marks are rewritten on a global scale, and retrotransposons are allowed to be strikingly active and roam more freely than at any other stage of mammalian life – all factors that can threaten the integrity of the genome (Bhowmick, Lerdrup, Mol Cell, 2022; Sankar, Lerdrup, Manaf et al, Nat Cell Biol, 2020; Dahl et al, Nature, 2016, Manaf, Lerdrup et al, submitted).
Our work has also led to development of a comprehensive software suite for data analysis to increase productivity and deeper understanding of genome-wide data (Lerdrup et al, Nat Struct Mol Biol, 2016, http://easeq.net).
- Establishment of new single-cell and low-input genome-wide methods
- Identification of causes for replication stress in the early mammalian embryo
- Identification of factors instructing the changes in the remarkably different oocyte and embryo epigenome