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1. (WO2017214379) SIMULATION DE CELLULE VIVANTE IN SILICO
Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

CLAIMS

What is claimed is:

1. A system comprising:

an incubator containing a microorganism, wherein the incubator is controllable to subject the microorganism to different environmental conditions that promote or inhibit growth of the microorganism, wherein growth of the microorganism is associated with the microorganism taking in or releasing a substance, and wherein each instance of the microorganism includes a plurality of constituents:

a sensor coupled to the incubator, wherein the sensor is operable to measure at least one external characteristic of the microorganism, wherein the at least one external characteristic includes an amount of the microorganism in the incubator or an amount of the substance in the incubator;

an automated laboratory, wherein the automated laboratory is operable to measure at least one internal characteristic of the microorganism, wherein the at least one internal characteristic includes an amount of one of the constituents or a degree of interaction between two or more of the constituents;

a controller, wherein the controller is operably coupled to the incubator, the incubator sensor, and the automated laboratory, wherein the controller comprises a computing device programmed to perform operations comprising:

controlling the incubator to subject the microorganism to a specified set of environmental conditions during a specified test period;

operating the sensor to obtain one or more measurements indicative of the at least one external characteristic of the microorganism during the specified test period; accessing a model of the microorganism, wherein the model predicts a response of the microorganism to the specified set of environmental conditions during the specified test period based on a plurality of adjustable parameters;

determining that at least one parameter of the plurality of adjustable parameters can be adjusted such that the predicted response of the microorganism to the specified set of environmental conditions during the specified test period corresponds to the one or more measurements obtained by the sensor, wherein the at least one parameter relates to the at least one internal characteristic of the microorganism; and

operating the automated laboratory to measure the at least one internal characteristic of the microorganism.

2. The system of claim 1, wherein the operations further comprise updating the model of the microorganism based on the measured at least one internal characteristic of the microorganism.

3. The system of claim 2, wherein controlling the incubator to subject the microorganism to a specified set of environmental conditions during a specified test period comprises controlling the incubator to subject the microorganism to a first specified set of environmental conditions during a first specified test period, wherein operating the sensor to obtain one or more measurements indicative of the at least one external characteristic of the microorganism during the specified test period comprises operating the sensor to obtain one or more measurements indicative of the at least one external characteristic of the microorganism during the first specified test period, and wherein the operations further comprise:

controlling the incubator to subject the microorganism to a second specified set of environmental conditions during a second specified test period;

operating the sensor to obtain one or more measurements indicative of the at least one externa] characteristic of the microorganism during the second specified test period;

determining that a further at least one parameter of the plurality of adjustable parameters of the updated model can be adjusted such that the predicted response of the microorganism to the second specified set of environmental conditions during the second specified test period corresponds to the one or more measurements obtained by the sensor during the second specified test period, wherein the at least one parameter of the updated model relates to the further at least one internal characteristic of the microorganism; and

operating the automated laboratory to measure the further at least one internal characteristic of the microorganism.

4. The system of claim 2, wherein the microorganism releases the substance and wherein the operations further comprise:

determining, based on the updated model, a modification of the specified set of environmental conditions to increase an amount of the substance produced by the microorganism; and

controlling the incubator to subject the microorganism to the determined modified set of environmental conditions during a further test period.

5. The system of claim 2, wherein the microorganism releases the substance and wherein the operations further comprise:

determining, based on the updated model, a modification of a genome of the microorganism to increase an amo unt of the su bstance produced by the microorganism; and

controlling the incubator to subject a sample of the microorganism having the modified genome to the specified set of environmental conditions during a further test period.

6. The system of claim. 1, wherein controlling the incubator to subject the microorganism to a specified set of environmental conditions during a specified test period comprises controlling the incubator to subject a first sample of the microorganism to a first specified set of environmental conditions during a first specified test period, wherein operating the sensor to obtain one or more measurements indicative of the at least one external characteristic of the microorganism during the specified test period comprises operating the sensor to obtain one or more measurements indicative of the at least one external characteristic of the first sampl e of the microorganism during the first specified test period, and wherein the operations further comprise:

controlling the incubator to subject a second sample of the microorganism to a second specified set of environmental conditions during a second specified test period; and

operating the sensor to obtain one or more measurements indicative of the at least one externa] characteristic of the second sample of the microorganism during the second specified test period, wherein determining that at least one parameter of the plurality of adjustable parameters can be adjusted such that the predicted response of the microorganism to the specified set of environmental conditions during the specified test period corresponds to the one or more measurements obtained by the sensor comprises determining that at least one parameter of the plurality of adjustable parameters can be adjusted such that the predicted response of the microorganism, to the first specified set of environmental conditions during the first specified test period corresponds to the one or more measurements obtained by the sensor of the first sample and further such that the predicted response of the microorganism to the second specified set of environmental conditions during the second specified test period corresponds to the one or more measurements obtained by the sensor of the second sample.

7. The system of claim 6, wherein the first specified set of environmental conditions and the second specified set of environmental conditions differ.

8. The system of claim 6, wherein the fi rst sample of the microorganism, and the second sample of the microorganism differ with respect to a genome of the microorganism,

9. The system of claim 1, wherein the automated laboratory comprises means for fluorescently imaging one or more instances of the microorganism to measure an amount of a substance in the microorganism.

10. The system of claim 1, wherein the automated laboratory comprises a microscope that is operable to determine a number of instances of a constituent of the

microorganism that are present in one or more instances of the microorganism.

11. The system of claim i, wherein the automated laboratory comprises means for measuring a number of instances of one or more specified sequences of RNA that are present in one or more instances of the microorganism.

12. The system of claim 1, wherein the automated laboratory comprises means for separating contents of one or more instances of the microorganism.

13. A method compris ing :

subjecting a microorganism, in an incubator, to a specified set of environmental conditions that promote or inhibit growth of the microorganism during a specified test period, wherein growth of the microorgan sm is associated with the microorganism taking in or releasing a substance, and wherein each instance of the microorganism includes a plurality of constituents;

operating a sensor to obtain one or more measurements indicative of at least one external characteristic of the microorganism during the specified test period, wherein the sensor is coupled to the incubator, and wherein the at least one external characteristic includes an amount of the microorganism in the incubator or an amount of the substance in the incubator; accessing a m odel of the microorgani sm, wherein the model predicts a response of the microorganism to the specified set of environmental conditions during the specified test period based on a plurality of adjustable parameters;

determining that at least one parameter of the plurality of adjustable parameters can be adjusted such that the predicted response of the microorganism to the specified set of environmental conditions during the specified test period corresponds to the one or more measurements obtained by the sensor, wherein the at least one parameter relates to at least one internal characteristic of the microorganism, and wherei n the at least one internal characteristic includes an amount of one of the constituents or a degree of interaction between two or more of the constituents; and

operating an automated laboratory to measure the at least one internal characteristic of the microorganism.

14. The method of claim 13, further comprising:

updating the model of the microorganism based on the measured at least one internal characteristic of the microorganism.

15. The method of claim 14, wherein subjecting a microorganism to a specified set of environmental conditions that promote or inhibit growth of the microorganism during a specified test period comprises subjecting the microorganism to a first specified set of

environmental conditions during a first specified test period, wherein operating a sensor to obtain one or more measurements indicative of at least one external characteristic of the microorganism during the specified test period comprises operating the sensor to obtain one or more measurements indicative of the at least one exteraal characteristic of the microorganism during the first specified test period, and wherein the method further comprises:

subjecting the microorganism to a second specified set of environmental conditions during a second specified test period;

operating the sensor to obtain one or more measurements indicative of the at least one external characteristic of the microorganism during the second specified test period;

determining that a further at least one parameter of the plurality of adjustable parameters of the updated model can be adjusted such that the predicted response of the microorganism to the second specified set of environmental conditions during the second specified test period corresponds to the one or more measurements obtained by the sensor during the second specified test period, wherein the at least one parameter of the updated model relates to the further at least one internal characteristic of the microorganism; and

operating the automated laboratory to measure the further at least one internal characteristic of the microorganism..

16. The method of claim 14, wherein the microorganism releases the substance and wherein the method further comprises:

determining, based on the updated model, a modification of the specified set of environmental conditions to increase an amount of the substance produced by the microorganism; and

subjecting the microorganism to the determined modified set of environmental conditions during a further test period.

17. The method of claim 14, wherein the microorganism releases the substance and wherein the method further comprises:

determining, based on the updated model, a modification of a genome of the microorganism to increase an amount of the substance produced by the microorganism.; and subjecting a sample of the microorganism having the modified genome, in the incubator, to the specified set of environmental conditions during a further test period.

18. The method of claim 13, wherein subjecting a microorganism to a specified set of environmental conditions that promote or inhibit growth of the microorganism during a specified test period comprises subjecting a first sample of the microorganism to a first specified set of environmental conditions during a first specified test period, wherein operating a sensor to obtain one or more measurements indicative of at least one external characteristic of the microorganism during the specified test period comprises operating the sensor to obtain one or more measurements indicative of the at least one external characteristic of the first sample of the microorganism during the first specified test period, and wherein the method further comprises:

subjecting a second sample of the microorganism to a second specified set of environmental conditions during a second specified test period; and

operating the sensor to obtain one or more measurements indicative of the at least one external characteristic of the second sample of the microorganism during the second specified test period, wherein determining that at least one parameter of the plurality of adjustable parameters can be adjusted such that the predicted response of the microorganism to the specified set of environmental conditions during the specified test period corresponds to the one or more measurements obtained by the sensor comprises determining that at least one parameter of the plurality of adjustable parameters can be adjusted such that the predicted response of the first sample of the microorganism to the first specified set of environmental conditions during the first specified test period corresponds to the one or more measurements obtained by the sensor of the first sample and further such that the predicted response of the second sample of the microorganism to the second specified set of environmental conditions during the second specified test period corresponds to the one or more measurements obtained by the sensor of the second sample.

19. The method of claim 18, wherein the first specified set of environmental conditions and the second specified set of environmental conditions differ.

20. The method of claim 18, wherein the first sample of the microorganism and the second sample of the microorganism differ with respect to a genome of the microorganism.