Séastien Lemire
Post.doc.
Phonebook
Research
Read more about my research here: Towards new antibiotics using Salmonella as a model pathogen: Metabolic modelling, high throughput genetics and phages
Personal
I arrived in Denmark in May 2007 after a PhD in the lab of Lionelllo Bossi in Gif-Sur-Yvette, France and 2 years of post-doc in the lab of Tetsuro Yonesaki at Osaka University, Japan. I have also worked in the USA during my master’s degree and that’s where the virus for phages got me and that I got hooked up by the genetics approach to biological questions.
There are two main families of phages : the lytic and the lysogenic or temperate phages. I call them phages but remember they are just viruses and actually not so different from those that regularly give you throat ache, enetritidis or worse diseases.
Lytic phages have a relatively simple life style : they infect a cell, kill it, use all of its ressources to multiply and finally lyse it liberate phages. That apparent simplicty is nevertheless hiding a much deeper level of interaction with their host population. Most lytic phages are capable of sensing the health of their host and the number of phages that are in the immediate vicinity and may decide to delay their reproduction up to several days if conditiosn are not optimal. The model organisms in that family are coliphage T4 or T7 but diversity is crucial and these actually account for most of the biosphere on Earth number wise. It is estimated that the Earth carries between 1030 and 1031 phages on Earth. We, humans, are only about 6.109.
Lysogenic phages have a more elaborate life-style being capable of alternating between a lytic and a dormant state where the bacteriophage genome is silenced but efficiently maintained, in most of the cases through integration inside of the bacterial chromosome. In the dormant, lysogenic state most phage genes are inactive and are transcribed only a repressor function (that keeps other genes silent) and a few “morons” that have non phage functions (addiction modules, virulence genes, super infection exclusion mechanisms…). The then so-called prophage can nevertheless be reactivated when properly stimulated, i. e. through DNA damage. This process known as induction releaves the silencing effect of the repressor through various mecanisms and resumes lytic growth. The regulation of lysogeny establishment and induction has been studied with phage lambda as a model for over 60 years but is still very mysterious as soon as phages other than lambda are considered and recent work shows that even within the cousins of lambda, there are still lots of surprises to be uncovered.
I am still fascinated by the incredible diversity of phages and the intricate relationships they establish with their hosts. How comes some bacteria tolerate up to about 25 of these potentially deleterious, “selfish” genetic elements that could kill them at any time ? What are the selective pressure to keep them alive and well ? Why do some bacteria only harbor degenerated prophages while other highly related bugs harbor a plethora of activa prophages happily lysing the cell as soon as it is stressed ? How does lysogenic regulation evolve ?
The rising of genomics will undoubtly help in answering at least some of these questions.
OK I love phages but this is not all I am interested in. Bacterial virulence is also another point that tickels my curiosity a lot. When thinking about it, it is for the same reasons as for phages : interactions between two organisms and the fight for a balance between predation and exhaustion of your preys which is I guess a general them in nature. This delicate balance is particularly apparent in Salmonella. There are over 2500 serovars of Salmonella enterica enterica subspecies I which is responsible for most of the warm blooded animal infections and they show variable degrees of host adaptation. Some serovars are generalists. They will infect close to anything as long as its warm, from primates to birds (Typhimurium, enteritidis, Hadar…) but other serovars are extremely host restricted and will only colonize a given host. Serovar Typhi/Paratyphi cannot infect anything else but primates and is even particularly efficient at infecting humans. Gallinarum will only infect fowl. What drives this niche adaptation and what gene(s) govern it is still not understood despite more than 60 years of study and the fact we have genomic sequences available. This is mystery which I am particularly keen on adressing.
Considering the number of projects I get myself into (eternal curiosity), I am surprized I manage to give myself some freetime, but I do. When that happens, I try to spend it with my son educating him in loving nature and enjoying the simple pleasures of a stroll along the lake, a ride through the forest or a trek along an alpine ridge…
We we shall climb Denmark’s highest point : Møllehøj (170.86 m) some day!
NOTE : This is a draft page which will be enriched as weeks pass by so please come back !
Student projects
Hassan’s project title : Identification of targets for antimicrobials in Salmonella typhimurium.
Keywords: Genome scale model, metabolic redundancy, synthetic promoter library, rate analysis.
Techniques used: Computer simulation, gene deletion, molecular cloning, microarray analysis.
Carmen’s project title : Contribution of prophages to the mutagenic response to DNA damage.
Keywords : prophage, umuDC, SOS response, error prone replication
Techniques used : bacterial genetics, cloning, recombineering
Potential available projects :
Please check here